Ada dua tahapan produksi Doxycycline

Bioproses

Proses ini bertujuan untuk menghasilkan Oxytetracyclines

1. A fermentative process for the production of oxytetracycline which comprises fermenting a nutrient
broth under aerobic conditions at a temperature between 22 DEG and 30 DEG C. by a mutant of
Streptomyces alboflavus (Waksmann & Curtis), and recovering accumulated oxytetracycline from the
fermented broth

https://www.google.ch/patents/US3637463

Kimiawi

Oxytetracyclines diproses menjadi Methacyclines

Methacylines diproses menjadi Doxycycline

1. A process for the synthesis of alpha -6-deoxy-5-hydroxytetracycline, a broad-spectrum antibiotic, by

reduction of 6-methylene-5-hydroxytetracycline using cobalt carbonyl, triphenyl phosphine and
hydrochloric acid in a reaction solvent and inert atmosphere.

https://www.google.com/patents/US3907890

2. 1. A process for the preparation of -6-deoxy-tetracyclines by the stereoselective heterogeneous

hydrogenation of a 6-demethyl-6-deoxy-6-methylene-tetracycline or an acid addition salt thereof, in the
presence of a tertiary phosphine, or the simultaneous dehalogenation and stereoselective hydrogenation
of an lla-halo-6-demethyl-6-deoxy-6-methylene-tetracycline or an acid addition salt thereof, in the
presence of a tertiary phosphine, characterised by the use of a rhodium salt catalyst, wherein the rhodium
is bonded to an aminopolysiloxane.

https://www.google.ch/patents/US4597904

Proses Purifikasi

1. A process for the recovery of -6-deoxy-5-hydroxytetracycline in high purity from the crude reaction
mixture resulting from the conversion of an intermediate into said -6-deoxy-5-hydroxytetracycline and
having the same as well as reaction by-products, degradation products and the -isomer as impurities,
said crude reaction mixture being the initial reaction mixture in which the -6-deoxy-5-hydroxytetracycline
is present prior to the institution of any recovery procedures, which consists essentially of the steps of (1)
first acidifying said crude reaction mixture with a concentrated aqueous solution of methanesulfonic acid,
sulphuric acid or hydrochloric acid, (2) then heating to a temperature of 60 to 90 C until said impurities
are further degraded, (3) cooling said reaction mixture and then (4) precipitating said -6-deoxy-5-
hydroxytetracycline from said reaction mixture thus treated and cooled, in the form of water insoluble acid
addition salts and molecular complexes selected from the group consisting of 5-sulfosalicylate, N,N'-
dibenzylethylenediamine- and N,N'-dibenzylethylenediimine molecular complexes, N,N'-
dibenzylethylenediamine alkaline earth metal and, N,N'dibenzylethylenediimine alkaline earth metal
molecular complexes by adding the corresponding acid or molecular complex to said treated and cooled
reaction mixture, said steps (1) - (4) being carried out sequentially without any intervening steps.

https://www.google.ch/patents/US4061676