25-hydroxydihydrotachysterol2 an innovative synthesis of a key metabolite of dihydrotachysterol2

✍ Scribed by Jaap C. Hanekamp; Rob Boer Rookhuizen; Hendrik J.T. Bos; Lambert Brandsma

• Book ID: 104203404
• Publisher: Elsevier Science
• Year: 1992
• Tongue: French
• Weight: 898 KB
• Volume: 48
• Category: Article
• ISSN: 0040-4020
• DOI: 10.1016/s0040-4020(01)85618-0

✦ Synopsis

A new synthesis of 25-hydroxydihydrotachysterol2 is described. The hydroxylated side-chain is constructed stereoselectively using a chiral Wittig reagent. The A-ring synthon is introduced utilising the Wittig-Homer method as developed by Lythgoe et al. The preparation of the metabolite is carried out in 18 steps. J. C. HANEKAMP er al. RESULTS and DISCUSSION a. Starting compound: the Wittig reagent. The required phosphonium salt for the construction of the 25-hydroxylated DHT, side-chain is depicted in scheme 1 (compound 1). The synthesis of 1 is already mentioned (in short) in our recently published report.*l The preparation was done in four steps, starting from 2 in a 73% overall yield. Synthetic and spectroscopic details of compound 1 (and related compounds) were published recently!2g13 Hodco Me 2 -Ho+oH-'+oH _ 'h3y+oH 2 3 4 Scheme 1.

b.

Starting compound: the CD synthon aldehyde. I4 A simple and straightforward synthetic route towards an appropriate CD synthon was chosen. Keto-aldehyde 5 (figure ) which was