H. B. Henbest

Abstract: THE last ten years have seen a concentrated effort in the partial and total synthesis of steroids, occasioned in particular by the discovery of the adrenocortical hormones and of their physiological activity. This effort has involved conducting selective reactions on multifunctional compounds, and protection of one type of functional group against the consequence of reactions aimed at another. It seems desirable to give a review of such selective reactions and modifications; not only for the benefit of workers in the steroid field itself, but also as a guide for those working in other fields of organic synthesis, some of whom tend to assume that steroid chemistry is an exclusive domain. This review covers the more important literature from 1948 through 1957, but it is not intended to be exhaustive. Work on tricyclic intermediates in steroid total synthesis has been included, but facts published in communication form are not dealt with unless such communications mention a modicum of experimental detail.

Abstract: Primary alcohols were selectively tetrahydropyranylated in good to excellent yields at room temperature using PdCl 2 (CH 3 CN) 2 as catalyst in tetrahydrofuran (THF) in the presence of phenols, secondary, and tertiary alcohols. The tetrahydropyranyl (THP) group could be efficiently removed using PdCl 2 (CH 3 CN) 2 as catalyst in CH 3 CN, while other protection groups such as p -toluenesulfonyl (Ts), tert -butyldiphenylsilyl (TBDPS), benzyloxycarbonyl (Cbz), allyl, benzyl (Bn), and benzoyl (Bz) remained intact under these conditions.

Abstract: Evidence was recently presented that an essential part of the accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is due to acceleration of a novel pathway, involving 7 alpha-hydroxylated intermediates in bile acid biosynthesis as precursors (J. Clin. Invest. 1985; 75:448-456). Such intermediates accumulate in patients with cerebrotendinous xanthomatosis due to lack of the mitochondrial 26-hydroxylase involved in the major pathway for bile acid biosynthesis. The new pathway may involve the following steps: 7 alpha-hydroxycholesterol----7 alpha-hydroxy-4-cholesten-3-one----cholesta-4,6- dien-3-one----4-cholesten-3-one----cholestanol. Accurate methods have been developed for assay of 7 alpha-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one in serum, based on isotope dilution-mass spectrometry. The serum levels of 7 alpha-hydroxy-4-cholesten-3-one as well as those of cholesta-4,6-dien-3-one were found to be markedly elevated in the three patients with cerebrotendinous xanthomatosis. Treatment of two of the patients with chenodeoxycholic acid reduced the serum levels of the two steroids by more than 80%. The concentration of cholestanol was reduced by 72% in one patient and by 48% in the other. The possibility is discussed that accumulation of cholestanol in patients with cerebrotendinous xanthomatosis is secondary to accumulation of 7 alpha-hydroxy-4-cholesten-3-one and cholesta-4,6-dien-3-one.

Abstract: Hydroxyl compounds readily add to dihydropyran in presence of a catalytic amount of ceric ammonium nitrate to give high yield of tetrahydropyranyl ethers.

Abstract: Acid-catalysed addition of isobutene to steroidal alcohols gives the t-butyl ethers in high yields. These ethers are acid-labile, but alkali-resistant. The t-butyl group is readily split off with trifluoroacetic acid. The usefulness of the method is demonstrated by a simple synthesis of testosterone benzoate from dehydroepiandrosterone.