3-Deoxy steroids

A similar synthesis starts from commercially available 1,5-hexadiyne and 2-methyl-cyclopent-2-enone. The benzocyclobutene is obtained from a bis-acetylene in a cobalt-catalyzed reaction. It rearranges regio- and stereoselectively to a 3-deoxy steroid derivative. The overall yield from the cyclopentenone was 40% (R.L. Funk, 1977). 

Steroids. XI. Metabolism of 3-Deoxy Steroids. 4. Determination of Urinary Metabolites of 3-Deoxy-estrone by Gas Chromatography Chem. Pharm. Bull. 18(10) 2119-2122 (1970) CA 74 9952x... 

The aromatization observed by Birch et al. (1965), involving loss of a molecule of methanol on condensation of 1-methoxycyclohexa-1,4-diene or its derivatives with M(CO)g (M = Cr, Mo, W), has been applied to the synthesis of 3-deoxy steroid hormones (Birch et al, 1966). 

The extract is washed with water, dried over sodium sulfate and the solvent evaporated. The yield of deoxy steroid is generally greater than 90% for sterically unhindered ketones. 

Steroidal ketones are converted into gew-difluoro steroids in moderate to good yield by treatment with sulfur tetrafluoride and anhydrous hydrogen fluoride, usually in an inert solvent, at ambient or close to ambient temperature. The order of decreasing reactivity of steroidal carbonyl functions towards the sulfur tetrafluoride/hydrogen fluoride reagent is as follows 3-oxo = 6-formyl > 17-oxo > 20-oxo of an 11.20-dioxo steroid > 20-oxo of an 11-deoxy steroid > conjugated 3-oxo > 11-oxo.72... 

Moriniere, M., and Boillereau, N. Qualitative and Quantitative Analysis of Urinary 17-Oxo Steroids and 20-Hydroxy- 2 1-Deoxy Steroids by Gas Chromatography and Mass Spectrometry Clin. Chim. Acta 52(3) 381-405 (1974) CA 81 60242n... 

In 1943, after being awarded the D.Sc. degree, Jeanloz was appointed as Research Associate, first with Meyer and then with Tadeusz Reichstein, Nobel Laureate for his work on steroid hormones. With Reichstein he studied the chemistry of deoxy sugars, some of which are constituents of these hormones, and developed3 a new method for the assay of these sugars. In 1946-1947 he spent 1 year in Canada as Research Associate at the University of Montreal, where he collaborated with D. A. Prins from the Research Division, Cleveland Clinic, Cleveland, OH, in the preparation of... 

Some 2-deoxy-analogues of rubrosterone have been reported.73 The synthesis commenced with a Bamford-Stevens reaction upon 3/3,17/3-diacetoxyandrost-5-en-7-one tosylhydrazone to yield the corresponding 5,7-diene. Successive chromic acid and selenium dioxide oxidation of this diene furnished the 2-deoxyrubrosterones (177 R1 = OAc, R2 = H, R3 = OH, X= 17/3-0Ac,H 5a-H) and (177 R = OAc, R2 = R3 = H, X = 17/3-OAc,H 5a-H) respectively. Alkaline hydrolysis of the latter derivative afforded an A-homo-B-nor-steroid (178). The rubrosterone (177 R1 = R2 = R3 = OH, X = O 5/3-H), which possesses antidiabetic activity, has been prepared by oxidative degradation of the cholestene (179), itself obtained from ecdy-sterone.74... 

This brief survey of natural products derived from the 3-deoxy-D-oro6iTk>-heptulosonic acid 7-phosphate pathway illustrates the economy of fimda-mental biosynthetic pathways. The relative economy and simplicity of the biological degradative and energy-yielding reactions is paralleled in the biosynthetic reactions. For example, 3-deoxy-D-oroW o-heptulosonic acid 7-phosphate is a precursor of a host of aromatic products mevalonic acid is the progenitor of the terpenoids and steroids, and 5-aminolevulinic acid of the porphyrins. 

If biotransformation experiments with selected microbial strains do not give satisfactory results with a particular compound, a chemically modified substrate should be considered. A methodology employed to prevent unwanted hydroxylation of a steroid is to block one face of the molecule by a large atom or group which can subsequently be removed. For example, side hydroxylations in positions 7a, 9a, and 14a were responsible for moderate yields in the 11 //-hydroxylation of 1 l-deoxy-17-hydroxycorticosterone with Curvularia lunata23. These undesired hydroxylations at the a-side of the molecule could be avoided by the use of the 17-acetylated substrate instead of the unprotected compound67. 

The first recorded 11/ -hydroxylation of a steroid was the transformation of 1 l-deoxy-17-hy-droxycorticosterone (1) into hydrocortisone (2) with Streptomyces fradiae205, albeit in very low yield. The first practical 11/J-hydroxylation processes were those using Curvularia lunala2 206 and Cunninghamella blakesleeana207-20R. The special strain, Curvularia lunata NRRL 2380, discovered via extensive screening operations, has continued to be important for the commercial production of hydrocortisone from 1. 

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