Synthesis of Aristotelia-Type Alkaloids. Part XV. Total synthesis of (+)-hobartinol

✍ Scribed by Markus Dobler; James C. Anderson; Mathias Juch; Hans-Jürg Borschberg

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: German
• Weight: 565 KB
• Volume: 78
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19950780204

✦ Synopsis

Synthetic (+)-makomakine (6) was transformed in six steps into (+)-( 17 R,18R)-17,18-dihydrohobartine-17,18-diol((+)-5) with an overall yield of 38 % (Scheme 2). This compound was shown to be identical with natural hobartinol, a monoterpene indole alkaloid from Aristoteliu uustrulusicu, originally believed to be the (17S)-epimer 1. At the same time, the synthesis of (+)-5 delineates the hitherto unknown absolute configuration of this metabolite. ') Part XIV: see [I]. *) ') 4, Taken in part from the diploma theses of J . C. A . [2], participant of the Imperial College (London)/ETH exchange scheme, and M . J . [3]. The authors would like to thank Prof. H.-P. Husson for providing them with a copy of this thesis.

During the presumed transformation of 1 into 2, the intermediacy of 3 was iiivoked [4]. However, at least in the most stable conformation of 3, the two centers of interest (0-C(17) and O=C-N( )) seem too far apart for a significant interaction. Furthermore, amide 3 conceivably is thermodynamically more stable than ester 2, so there is no obvious reason why the N-acetyl derivative 3 should rearrange to the latter.