A TOTAL SYNTHESIS OF COLCHICINE*

R. B. WOODWARD

Department of Chemistry, Harvard University,

Cambridge, Massachusetts

HE highly toxic properties of the meadow saffron, or autumn

T crocus ( Colchicum autumnale L.) , were well known to the
ancient Greeks. The plant appears to have been one of the in­
struments of the odious Medea, daughter of a ruler of the Trans­
caucasian kingdom of Colchis, and its use in the black arts was
described by Dioscorides in 78 A.D. By Byzantine times, its more
beneficial utility in the e ffective symptomatic treatment of acute
gout had been recognized. Mor e recently, in this century, the ac­
tive prin ciple, colchicine, was found to possess a remarkable
capacity for arresting cell division, and this discovery has led to
numerous advances in cytology and plant phys iology .
Colchicine was isolated for the first time in a more or less pure
state in 1820 by Pelletier and Caventou-those same great pio­
neers who deprived quinine, strychnine, veratrine, and many other
substances of their hiding places. Serious structural studies were
commenced in 1880 by Zeise!, and were continued in this century
by many investigators, among whom Windaus played a leading
role, but the conclusions from the work were mired in miscon­
ceptions until a brilliant inspiration of Dewar set the stage for
the establishment of the correct structure (I) i n 1949. This

Meo
NHCOCH3

Meo

Meo

Meo

*Lecture delivered October 17, 1963.

31
32 R. B. WOOD'\VJARD

molecular array is not especially complicated when compared

with those of many well-known natural substances. In particular,
the stereochemical situation is very simple in that the molecule
is possessed of only a single asymmetric center (starred) . But
the structure does possess some very unusual features, of which
the 7-membered ring B, and more particularly the tropolonoid
ring C, deserve special mention. It was this latter construct which
Dewar's imagination brought to 1 ight, and its recognition led
directly to the development of a wholly new and fascinating
chapter of organic chemistry. The episode is worthy of special
mention for its powerful illustration of the impact which the
study of individual natural products has frequently had upon the
development of fundamental aspects of the science of organic
chemistry.
The colchicine structure is sufficiently extraordinary to have
attracted widespread attention as a synthetic objective, and three
of the many ensuing investigations have eventuated in success­
those led by Eschenmoser in Switzerland (cf. Schreiber et al.,
1959, 1961), van Tamelen in this country (cf. van Tamelen
et al., 1959, 1961), and Nakamura in Japan (cf. Nakamura,
1962; Nakamura et al., 1962; Sunagawa et al., 1962). I shall
describe the completion of yet another synthesis of colchicine,
and in so doing I hope that I may be able to illustrate in a general
way something of the methods of the synthetic chemistry of the
present day, and of the spirit in which they are applied.
The synthesis of a molecule of any complexity must necessarily
be a sequential process, the successful issue of which is dependent
upon the favorable outcome of each of an often very considerable
number of separate, consecutive stages. Consequently, the first
preoccupation of a would-be artificer in this field must be plan­
ning, on a scale which is neither possible nor desirable in many
other areas of chemical exploration. The plan should be such that
each projected operat i o n is based as fi rmly as possible upon es­
tablished chemical principJes, or matters of fact, and yet, since
the way is certain to be largely uncharted in matters of detail,
it must be sufficiently flexible to permit changes of course, should
insuperable obstacles be encountered. But within these limitations,
although the spe c ifi c objective in synthetic work is defined with
unique precision, the manner of reaching it most emphatically is
 A TOTAL SYNTHESIS OF COLCHICINE 33

not. It would be poss i ble to synthesize a mol ecu l e like colchicine

in countless different ways, no one of which would resemble any
other except in its outcome. Much of the charm and fascination
of this kind of work 1 i es in the free rein which t h e imaginat i on
may be permitted in planning the adventure, and as we l l in ex­
ecuting it. In these circumstances it may come as no surprise that
the basic element in our entire work on the synthesis of colchicine
is a molecular construct which is in no wise e ith er demanded by,
or even suggested by, the colchicine structure. This latter con­
tains one nitrogen atom, incor p orated as an acetylamino group.
A nitrogen atom, in most of th e modes in which it can be situated
in or ganic molecules, is a reactive s ite to which new bond s may
,

read il y be made th rough interaction with other molecules, or

especially easily thr ough interaction with other atomic gro upi ngs
within the same mol ecu l e For these reasons, the presence of a
.

nitrogen atom in synthetic intermediates may compl icat e synthe tic

operations, through the opportunities that ve r sati le ato m prov ides
for reactions which may supersede desired changes--changes
which might well take place smoothly in the absence of the reac­
tive offender. Consequently, we wished to devise some way in
which the nitrogen atom of our pro j ected colchicine molecule
would be embedded in an environment which rendered it unre­
active and inoffensive. But we hoped for more than that. We
hoped that we could conceal its reactivity, and at the same time,
in so doing, build it into an array which would further exhibit
special characteristics of positive value in fac ilita ting our archi­
tectural effort. These t h ings we imagined we m ight accomplish
through choosing as our basic s yn thetic intermediate a substance
containing the isothiazole ring (II). In such a ring the bonding
capacities of the nitrogen atom are virtually fully utilized. Even
the remaining unshared electron pair on the n itrogen atom would

Meo

C)
Meo

OH
II III
34 R. B. WOODWARD

be expected to be coaxed into reaction only with great difficulty,

since the normal already limited availability of such electrons in
aromatic heterocyclic systems should be further diminished by the
attachment of the nitrogen atom to the electron-attracting sulfur
atom. The whole isothiazole ring should represent a very stable
aromatic system, not subject to ready modification, and hence able
to withstand chemical operations of some severity. Furthermore,
the ring should be rigid, and thus provide a favorable platform
for the construction of yet further rings. Finally, the placement
within the ring of nitrogen and sulfur atoms might well be ex­
pected to exert, upon attached groupings, specific activating in­
fluences, of which advantage might be taken for constructing new
bonds in desired directions. All of these factors led us to suppose
that we might be able to elaborate a simple isothiazole to a
molecule such as (III), without interference from the tamed
nitrogen atom, and indeed with positive assistance from special
properties of the isothiazole ring. Of course, even assuming the
successful outcome of such operations, it would be necessary sub­
sequently to disabuse the molecule (III) of its sulfur atom, and
to effect certain other relatively simple operations in order to
complete the conversion of (III) into colchicine itself. But ex­
cellent methods are available for the removal of sulfur from
organic molecules, and we were confident that they could be put
to use in a terminal stage of our investigation.
One aspect of our plan to base a synthesis of colchicine upon a
simple isothiazole intermediate might well have given us pause.
A forceful reminder of the fantastic multiformity of organic
chemistry is provided by the fact that although literally millions
of different organic molecules were known at the time our plan
was laid down, no simple isothiazole of any kind had been pre­
pared! Consequently we first set about to see ·whether we could
coax a member of the class into being. We chose to investigate
the reaction of methyl-.B-aminocrotonate (IV) with thiophos­
gene, expecting that the strongly electrophilic carbon atom of the
latter would attack the methyl-,B-aminocrotonate at its central
carbon atom, where electrons should be readily available, as a re­
sult of the presence within the molecule of the primary amino
group (V, arrows). The expected product (VI) was one which
 A TOTAL SYNTHESIS OF COLCHICINE 35

IV v

contains all of the atomse ce ssa ry for the construction of an

n

isothiazole ring, and we h oped that an oxidative process of some

kind might eventuate in the loss of two electro ns , and the forma­
tion of the desired new aromatic cycle, as in (VII) . In the event,

CH3 NH2 .cH3X?

XI s
::::;:;;-- N
'

MeOOC c� MeOOC � S
I
Cl Cl

VI VII

methyl-.fl-aminocrotonate was readily attacked by thiophosgene,

in ether solution in the presence of triethylamine, but to our
astonishment, the p roduct was not the a-thiocarbonyl compound
(VI) . It was rather the isothiazole (VIII) ! How had this most
surprising change come about? It still seemed most probable that

VIII

the initial union of the molecules had taken place to give the ex­
pected (VI), and in a general way it was clear that a kind of in­
ternal oxidation-reduction must have occurred-that is, that the
carbon-chlorine bond of (VI) had been reduced, at the expense
of the oxidation of the skeleton of the molecule, with concomitant
transformation of the latter to the stable aromatic isothiazole sys­
tem. In detail, one might postulate that the unshared electron
pair on the nitrogen atom attacks the sulfur atom directly, to give
the fugitive intermediate (IX) , from which one might imagine a
36 R. B. WOODWARD

H H
CH3 :Q N CH3 N
'\ '

MeOOC
I //':)
GCl
MeOOC D
I s

IX x

XI

chloride ion is lost, to give ( X) . This unusual, not to say bizarre,

construction may appear more palatable when it is written in the
alternative mode (XI), which further shows more clearly its re­
lation to the observed product (VIII), which may be produced
from it by protonation at C-5, accompanied by deprotonation at
the nitrogen atom. The direct attack of the nitrogen atom upon
sulfur is one of the unusual elements of this scheme, but it may
be helped by the special circumstance that the product of the
change already contains in a sense an aromatic sextet of electrons.
In any event, whatever the other virtues of the proposed scheme,
we have been unable to devise others which are in any measure
competitive in plausibility, and beyond that, it provided the basis
for a discovery which was of the first importance for our syn­
thetic work. Thus, we reasoned that if (XI) were an intermedi­
ate in the changes just discussed, it followed that a hydrogen atom
in the 5 position of an isothiazole ring should be readily remov­
able by basic reagents with the formation of a relatively stable
anion of the type (XII). This presumption was easily put to the
test, with positive outcome, when it was found that the isothiazole
(VIII), in heavy methanol solution in the presence of a small

XII XIII
 A TOTAL SYNTHESIS OF COLCHICINE 37

amount of sodium methoxide, was smoothly converted to the cor­

responding deuterated s pec i es (XIII). Clearly, the possibility of
generating readily an anionoid reactive site at the 5 position of
5-unsubstituted isothiazole derivatives greatly increases the syn­
thetic opportunities inherent in such substances. It should be em­
phasized that this aspect of the reactivity of isothiazoles was not
anticipated, and indeed h as not even now been rat ional ized in
terms of .first principles. This history has, I hope, been worth de­
lineating in some detail, in view of the cogency of the example
which it provides of the frequent occurrence in synthetic work of
surprises which, properly accepted, augment synthetic potential­
iti es , and as well exte nd the bounda ries of fundamental knowl­
edge.
Thus, there was readily available to us in quantity the simple
isothiazole (VIII) , with its unobtrusive nitrogen atom buried in a

stable aromatic ring, and we could now begin to build upon this
firm base. At the very outset we were able to take advantage of
one of the positive fruits which we had hoped for in the pres­
ence of the isothiazole ring. The methyl group of our intermedi­
ate, situated as it is a to the carbon-nitrogen double bond of the
isothiazole system, would be expected to be activated by that s itu­
ation, and such was indeed found to be the case. When (VIII)
was treated with N-bromosuccinimide in carbon tetrachloride so­
lution in the presence of light, it was readily transformed into
the corresponding bromo compound (XIV) , which in its turn re-

XIV xv

¢3P=CHx:; �\
s
Meooc �

XVI
38 R. B. WOODWARD

acted smoothly with triphenylphosphine to give the quaternary

salt (XV). The stage was now set for the utilization of a Wittig
reaction, a general process discovered only a decade ago, and one
of the smoothest methods available for the construction of a car­
bon-carbon bond . Thus, when the phosphorane (XVI), pro­
duced from the phosphonium salt (XV) by the action of sodium
metho xide, was allowed to react with 3,4,5-trimethoxybenzalde­
hyde in hot absolute methanol, smooth combination occurred to
give (XVII), in which molecule the trimethoxybenzene moiety
of the cokhicine molecul e was now p ro perly set in pl ace Com­ .

p arison of the structure of the new intermediate (XVII) with

Meo Meo

Me o Meo

Meo Meo

XVII XVllI

that of the colchicine molecule reveals that a single carb on carbon -

bond is wanted where a double bond is p resent, and this detail

was dealt with through reducing (XVII) to (XVIII) , using
hydrazine in the presence of hydrogen peroxide and a small
amount of cup ric ion. Only recently brought to light by the in­
dependent studies of Corey, van Tamelen, and Hiinig, this valu­
able method of reduction in which the intermediacy of the fugi­
,

tive molecule diimide is assumed, was of very special merit in our

case, since the catalytic methods ordinarily useful in the reduction
of unactivated multiple bonds would almost certainly be in­
appl icab le to a molecule containing a sulfur atom.

We now wished to forge onto (XVIII) furthe r atoms of the

projected colchicine molecule, and we had it in mind to utilize
the carbomethoxy grouping as a reactive site to whi ch such further
atoms could be attached. But we decided first to reduce the oxida­
tion level of the group to that which the correspond ing carbon
atom occupies in the colchicine molecule, and at the same time
augment its reactivity. These aims were most readily achieved by
reducing the ester, with lithium aluminum hydride, to the carbinol
(XIX) , and oxidizing the latter w ith manganese dioxide to the
 A TOTAL SYNTHESIS OF COLCHCCINE 39

Meo Meo

Meo Meo

Meo

XIX xx

¢3 P =CH· CH =CH· COO Me

XXI

aldehyde (XX) . The stage was now set for a further Wittig reac­
tion, in this case with the phosphorane ( XXI ) . The combination
of these two molecules gave a mixture of stereoisomeric
a, {3,y, o unsaturated esters, which was hydrolyzed by aqueous
sodium hydroxide, and irradiated with visible light in the pres­
ence of iodine, in order to convert each of the substances contain­
ing one or more cis-oriented double bonds to the same /rans­
isomer ( XXII) .
M eo

Meo

XXII

In ( XXII) , we had completed the assemblage of most of the

carbon atoms necessary for the construction of the colchicine
skeleton, and we were now in a position to elaborate one of the
unusual structural features of the molecule, namely the 7-mem­
bered ring B. Thus, we expected that the action of acidic re­
agents on the doubly unsaturated acid (XXII) would generate an
electron-deficient center at the terminus of the conjugated chain
(XXIII, arrows ) and that this center could attack an ortbo
position of the benzenoid ring, at which electrons are readily
40 R. B. WOOD\VARD

available for bond formation, in consequence of the attachment

to the a ro mat ic system of su itably disposed methoxyl groups.
While closures leading to 7-membered rings are frequently
a good deal less facile than tho se leadi ng to 5- or 6-mem­
bered rings, we had reason to s uppose that in our special case
the isothiazole r ing mi ght play a fur ther beneficial role, through
the rigidity which it introduces into the carbon chain whose ends
must be closed, and perhaps as well through the specific angles
enforced upon the isothiazole rin g carbon atoms. In t he event,
the unsaturated acid (XXII) was s moo thly isomerized by 70%
aqueous perchl oric acid at 60° to give the {3,y unsaturated acid
(XXIV). In this r eaction, again, the initial product was a mix-

Meo

Meo

HOOC

XX III XXIV

ture of acids, stereoisomeric about the carbon-carbon double bond ;

since the latter was in any case not a needed feat ure , it was re­
moved, again by di imide reduction, and the beautifully crystal­
line saturated acid (XXV) was obtai ned in go od yield as the
single product of the over-all series of reactions. One other point
is worthy of note in co nnection with this process for the con­
struction of ring B. It will be observed that the aromatic r in g to
which cyclization must be made contains two free ortho positions,
at either of which, attack of the electron-deficient center mi ght
occur. The symmetry of t he molecule is such, however, that attack
at either position leads to the same product.
It now remained to construct the second of the 7-membered
rings of the colchicine molecule. It will be recalled that we had
discovered, e arly in our work, that a hyd ro gen atom in the 5
position of an isothiazole ring can be removed easily by basic
 A TOTAL SYNTHESIS OF COLCHICINE 41

reagents, and it may now be noted that our intermediate (XXV)

contains such a hydrogen atom. It might therefore be imagined
that a direct base-catalyzed cyclization could be brought about
within the molecule of a suitable carboxyl-activated derivative of
(XXV) (cf. XXVI, arrows). However, it must be remembered

Meo Meo

Meo Meo

xxv XXVI

that such carbon-carbon bond-forming reactions are invariably re­

versible, and do not ordinarily proceed to completion unless the
product is withdrawn from the reaction milieu by a subsequent
change. In the light of these facts we considered it preferable to
utilize the anticipated reactivity of the 5 position of our isothiazole
( XXV) to introduce a further carbon atom, in order to prepare
the way for a cyclization of a known and relatively certain type.
This objective was achieved when the add (XXV) was treated
first with o-lithiobiphenyl in tetrahydrofuran, and then with
carbon dioxide, to give the dicarboxylic acid ( XXVII) . This
simple and effective step was most gratifying in that it represented
a highly useful realization of our newly discovered synthetic
potentialities of 5-unsubstituted isothiazoles. But although the de­
tails have no place h ere, it should be mentioned that the specific
factors which are crucial for bringing about the change success­
fully were determined only after a long period of arduous and
careful experimentation. With the di-acid ( XXVII) in hand,
the remaining stages in the construction of ring C proceeded
without incident. The acid was converted into the corresponding
dimethyl ester, which was cyclized in 90% yield, in dioxane solu­
tion, using sodium hydride as catalyst, to the ketoester (XXVIII),
which in its turn was smoothly hydrolyzed and decarboxylated, by
treatment with hot aqueous acetic and sulfuric acids, to the desired
ketone ( XXIX) .
42 R. B. WOODWARD

Meo Meo

MeO Meo

COOH

COOH COO Me

XX VII XXVIII
Meo

Meo

XXIX

Inspection of the colchicine structure will reveal that at this

point in our work we wished to introduce a second oxygen ad­
jacent to that present in the ketone (XXIX) . It may be noted at
the outset that we could reap at this point another advantage from
the presence of our isothiazole ring, in that one of the positions
adjacent to the carbonyl group was blocked by the heterocycle,
and we could be sure that any reaction which we might choose
could occur only at the desired site. Several methods were avail­
able for the introduction of a carbonyl group next to one already
present in an organic molecule, but none of them was entirely
satisfactory, and some of them involved reagents which might
well attack our molecule at points other than the desired
methylene group. Consequently, we chose at this stage to develop
an entirely new method, especially suited to the opportunities
and limitations inherent in the structure of our intermediate
(XXIX) . First, the ketone was transformed in high yield into
the corresponding a-hydroxymethylene compound (XXX) , by
condensation with ethyl formate in tetrahydrofuran in the pres­
ence of sodium hydride and a trace of alcohol. Then, treatment
of (XXX) with trimethylene-bis-p-toluenethiosulfonate in boil­
ing isopropyl alcohol in the presence of potassium acetate afforded
the dithian (XXXI) in high yield. This interesting reaction was
 A TOTAL SYNTHESIS OF COLCHICINE 43

Meo Meo

Meo MeO

CHOH

xxx XXXI

developed in our laboratory several years ago for the introduction

of a protecting or blocking group in place of an a-methylene
group whose reactivity posed an obstacle to the success£ul com­
pletion of reactions at an alternative site within a keton.e molecule.
When used in that way the protecting dithian grouping was easily
removed, using Raney nickel, after the desired changes had been
completed elsewhere. In the instance at hand, it was hoped that
the dithian grouping could be replaced, not with hydrogen, but
rather with oxygen, and such was indeed found to be the case.
When the dithian (XXXI) was treated with warm aqueous acetic
acid in the presence of mercuric acetate and a small amount of
aqueous perchloric acid, the beautifully crystalline, bright yellow
a-diketone (XXXII) was produced in high yield.

Meo MeO

Meo Meo

OAc
0

XX XII XXXIII

In order to complete the conversion of ring C in our diketone

( XXXII) to the required tropolone ring, it was now necessary
to remove two hydrogen atoms from the molecule. Here again a
number of methods had been used in simple cases for the direct
conversion of cycloheptane- and cycloheptene-diones to tropolones,
but again none of these processes proceeded in high yield nor
did they seem especially rational. We felt that it should be pos-
 44 R. B. WOODWARD

sible to take advantage of the aromatic stabilization within the

tropolone system to drive forward a dehydrogenation process and
render it facile, but we could not envisage any direct process, hav­
ing its origin in the diketone, in which the transition state for
dehydrogenation could be stabilized by its tropolonoid character.
Such a situation could, however, develop within a closely related
enol derivative such as (XXXIII) , and we set about to prepare
that substance, by treating the diketone with pyridine and acetic
anhydride. The reaction afforded a new, beautifully crystalline
substance, but it was an easy matter to show that it was not
the anticipated enol derivative (XXXIII) . No doubt (XXXIII)
was the initial product, but reaction had proceeded further to
give the dienol diacetate (XXXIV) ! Beyond that, this substance

Meo Meo

Meo Meo

AcO
OH

XX XIV xx xv

behaved in a most remarkable manner when it was subjected to

routine physical examination, in accord with our invariable prac­
tice with each of the intermediates I have described. In particular,
the ultraviolet absorption spectrum measured in alcohol solution
was not especially revealing, but when a drop of alkali was added,
marked changes occurred. Furthermore, the new spectrum was
not the rather uninteresting one of the diketone (XXXII) -the
anticipated product of simple hydrolysis of the enolacetate group­
ings of (XXXIV) , but rather possessed two new, well-defined,
very long wavelength bands. It was at once clear that an entirely
new chromophoric system had been generated, and but a short
step further to conclude that the new system was that of the de­
sired tropolone (XX.XV) ! While we make pretense to no virtue
beyond that of serendipity in relation to this most amiable acci­
dent, it is quite clear what had happened. Hydrolysis of the
 A TOTAL SYNTHESIS OF COLCHICINE 45

diacetyl derivative had led to the enediol dianion ( XXXVI) and

that species, like others of its class, had suffered loss of two elec­
trons to molecular oxygen, which, unless extreme precautions to
exclude it are taken, is always present in sufficient quantity to
serve that function at the low concentrations of substrate used
in spectroscopic measurements. The resulting diketone ( XXXVII)

Meo MeO

MeO Meo

XXXVI XXXVII

is of course simply a tautomeric modification of the tropolone

( XXXV) , into which it suffers ready isomerization. It was a
simple matter to adapt this conclusion to the development of a
very satisfactory method for the preparative conversion of
(XXXIV) to the tropolone (XXXV). And here we must point
out once again a vital role played by the isothiazole ring, in pro­
viding, in a concealed and unreactive, but nonetheless effective
form, one of the double bonds of the needed system.
Our investigation now entered a phase which was tinged with
melancholy. Our isothiazole ring had served admirably in every
anticipated capacity, and some others as well. With the obten­
tion of ( XXXV == III) , it had enabled us to construct the entire
colchicine skeleton, with almost all of the needed features properly
in place, and throughout the process, it and its concealed nitrogen
atom had withstood chemical operations, variegated in nature,
and in some instances of no little severity. It had mobilized its
special directive and reactive capacities dutifully, and had not once
obtruded a willful and diverting reactivity of its own. Now,
it must discharge but one more responsibility-to permit itself
gracefully to be dismantled, not to be used again until someone
might see another opportunity to adopt so useful a companion
on another synthetic adventure. And perform this final act with
46 R. B. WOODWARD

grace it did. When the tropolone ( XXXV), in aqueous sodium

hydroxide solution, was treated with Raney nickel for a short
time, the sulfur atom was readily stripped from the molecule.
In order to ensure complete reduction of the carbon-nitrogen
double bond, the reaction m ixture was reduced directly with
sodium borohydride, and to facilitate isolation of the product,
it was acylated with acetic anhydride and pyridine. After the re­
sulting material had been subjected to mild treatment with dilute
sodium hydroxide to hydrolyze any 0-acetyl compound which
might be present, racemic colchiceine ( XXXVIII) was isolated
Meo
NHCOCH3

Meo

Meo

0
OH

XX XVIII

in good yield. This material was shown to be identical in all re­

spects with an authentic sample of the same substance, which was
readily available from natural colchicine. Further, since the
methylation of the tropolone hyd roxyl group and the resolution
of the resulting racemic colchicine are reactions which had already
been established, working with natural materials, our synthesis of
colchicine was now complete.
One aspect of work of this kind hardly shows through a dry
account of the sort I have presented here, and deserves explicit
mention. Each of the intermediates along our progression to the
colchicine molecule is a beautifully crystalline substance, an en­
tirely new form of matter, persuaded into being in response to
the challenge of an often remote objective. It is delightful to work
with such things, and the delig ht which the experimenter
experiences in his manipulation contributes in no small ·meas­
ure to the skill required to create them. I had the good
fortune to be associated in this work with two exceptionally able
experimenters-Mr. Jack Gougoutas and Dr. Gert Volpp, and
I should like to take this opportunity to express my appreciation
 A TOTAL SYNTHESIS OF COLCHICINE 47

and admiration of their skill. It is to them that you are indebted

for what enjoyment you may have derived from my account of
their achievement. May I also express our thanks for the generous
support of our work by the National Institutes of Health.

REFERENCES

Nakamura, T. (1962). Chem. Pharm. Bull. (Tokyo) 10, 299.

Nakamura, T., Murase, Y., Hayashi, R., and Endo, Y. ( 1962). Chem. Pharm.
Bull. (Tokyo) 10, 281.
Schreiber, ]., Leimgruber, W., Pesaro, M., Schudel, P., and Eschenmoser, A.
(1959). Angew. Chem. 71, 637.
Schreiber, ]., Leimgruber, W., Pesaro, M., Schudel, P., Threlfall, T., and
Eschenmoser, A. (1961). Helv. Chim. Acta 44, 540.
Sunagawa, G., Nakamura, T., and Nakazawa, J. ( 1962). Chem. Phm·m. Bull.
(Tokyo) IO, 291.
va n Tamelen, E. E., Spencer, T. A., Jr., Allen, D. s., Jr., and Orvis, R. L.
( 1959). f. Am. Chem. Soc. 81, 6341.
van Tame Jen, E. E., Spencer, T. A., Jr., Allen, D. s., Jr., and Orvis, R. L.
(1961). Tetrahedrnn 14, 8.