Dehydroepiandrosterone (DHEA, 2) is an important endogenous steroid hormone in mammals used in the treatment of a variety of dysfunctions in female and male health, 1 as well as an intermediate in the synthesis of steroidal drugs, such as abiraterone acetate which is used for the treatment of prostate cancer. 2−4 In this manuscript we describe a novel, concise, and cost-efficient route toward DHEA (2) and DHEA acetate (3) from 4-androstene-3,17-dione (4-AD, 1). Crucial to success was the identification of a ketoreductase from Sphingomonas wittichii for the highly regio-and stereoselective reduction of the C3carbonyl group of 5-androstene-3,17-dione (5) to the required 3β-alcohol (2, >99% de). The enzyme displayed excellent robustness and solvent stability under high substrate concentrations (up to 150 g/L).

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NOTES 361Since the dispersion of both the refractivity and impurities. This study was prompted by the the Verdet constant is governed by the term observation that introduction of a small amount of ZAi/(vi2 -v2), constancy of the ratio A V / A n cis-1,2-dimethylcyclohexane as an impurity in 1,lwould be indicative of the fact that the electronic dimethylcyclohexane caused an increase in the transitions responsible for both are identical. The freezing point of the latter hydrocarbon, instead data in the last column show that this expecta-of the normal lowering. Although similar irtion is essentially fulfilled, as has also been found regularities caused by solid solution formation for various aliphatic oxygen compounds.s have been observed in several binary hydrocarbon systems studied in detail by 0 t h ~~r k e r~,~~ it was thought that this new information would SHELL DEVELOPMENT COMPANY EMERYVILLE, CALIF.RECEIVED MAY 24,1948 prove helpful because of the widespread reliance on cryoscopic data as criteria of purity. The results of this investigation are summarized

NOTES vol. 23 pressure; gas absorption was complete in 2.5 hr. The catalyst was removed by filtration and the solvent evaporated on the steam bath. The residue had n™°1.4790 and [«Id50 +15.2°. The dibenzylidene derivative had the m.p. 124-125°.(-\-)cis-8-Methylhydrindane (X). The ketone (IX) (3.5 g.) was refluxed for two hr. at 135°with 4.0 g. of potassium hydroxide, 80 ml. of diethyleneglycol, and 7.0 g. of 85% hydrazine hydrate. The water was distilled off and then the temperature was raised to 200°for 4 hr. The mixture was cooled, taken up in water, extracted with pentane, and the pentane layer washed with concentrated sulfuric acid until the acid no longer became colored. The pentane solution was washed with water, dried over magnesium sulfate, and the pentane removed, leaving two grams of an oil whose• infrared spectrum showed no carbonyl band and was identical with that given in ref. 7. The oil crystallized on cooling, m.p. 5°, [«Id60 +3°(6% in chloroform).Acknowledgment. We wish to thank Prof. Gilbert Stork for his help and interest in this work and as well, Prof. Carl Djerassi for the rotatory dispersion curves.