Patent GB-973143-A (GB)
Title: New hydroxy-aldehydes of the pregnane series and functional derivatives thereof and a process for their manufacture
IPC: C07J75/00
Filed: 1960-12-09
Abstract: The invention comprises (1) a process for the preparation of a 20-hydroxy-18-aldehyde of the pregnane series or an ester or ether of the 18, 20-semiacetal thereof, wherein an 18-unsubstituted-20-hydroxy-pregnane is treated with an oxidyzing lead acylate in the presence of iodine and the 18-iodo-18, 20-oxido product so obtained is hydrolyzed to an 18-hydroxy-18, 20-oxido compound or reacted with an alkali metal carboxylate in a neutral medium to give an 18-acyloxy-18,20-oxido compound or reacted with an alkali metal alcoholate to give an 18-ether of the 18-hydroxy-18, 20-oxido compound; and (2) the following 18-hydroxy-18, 20-oxido-steroids (reference to this grouping and optional groups being omitted from each name)-3a -hydroxy-5b -pregnanes, 3b -hydroxy-5a -pregnanes, D 5 - 3b  - hydroxy - pregnenes and D 4-3-oxo-pregnenes and their D 5-3-ketals, the 18-oxo-20-hydroxy-tautomers of these steroids, and esters, ethers and acetals thereof. In the hydrolysis process, which is preferably performed with an alkali metal acetate in aqueous acetic acid, bimolecular ethers containing an 18, 181-oxygen bridge may also be formed but these may be split to give the 18-hydroxy compounds again. 18-Acyloxy compounds and 18-ethers may be obtained from the 18-hydroxy compounds by acylation or etherification e.g. with alcohols or dihydropyran in the presence of an acid catalyst, and the 18-acylates may be hydrolyzed to give the 18-ols again.  Acylation in the presence of a Lewis acid results in the formation of 18, 18, 20-triacyloxy derivatives, which on mild acid hydrolysis give 20-acyloxy-18-aldehydes. The 18-aldehyde group can then be acetalized, the 20-acyloxy group can be hydrolyzed under alkaline conditions, and the 20-hydroxy group oxidized to the 20-oxo group. The starting materials for the present process may be of the pregnane or 19-nor-pregnane series and may contain free, esterified or etherified hydroxyl groups, free or ketalized oxo group, alkyl groups or halogen atoms as substituents in the ring system or 17-side chain, and they may also contain double bonds or oxido groups, for example starting from the 5-carbon atom and/or in the 9, 11-position. Particularly mentioned are 11-oxo, 11a  or b -hydroxy, 21-hydroxy and 16- and 20-methyl groups and D 1,4-double bonds in addition to those specified above. Detailed examples are given (a by-product in the oxidation of 3b -acetoxy-20b -hydroxy-5a -pregnane being 3b -acetoxy-20-hydroxy-18, 20-oxido-5a -pregnane) and an extensive list of esterifying carboxylic and sulphonic acids and etherifying alcohols is also provided.  18-Unsubstituted -20- hydroxy - pregnane compounds used as starting materials are obtained by reduction of the corresponding 20-keto compounds. D 5-3-ethylenedioxy-11a -acetoxy-20-hydroxy-pregnene is prepared by reducing 11a -acetoxy-progesterone and selectively oxidizing the product to give D 4-3-oxo-11a -acetoxy-20-hydroxy-pregnene, and then ketalizing this. D 5,9(11) - 3 - ethylenedioxy - 20 - hydroxy - pregnadiene is prepared similarly.  Specifications 973,144 and 973,145 are referred to.