STUDIES DIRECTED TOWARDS A TOTAL SYNTHESIS OF OLIVIN
Abstract
A method for the stereoselective synthesis of the C-ring and the polyoxygenated side chain at C(,3) of olivin 1 was investigated. A regio- and stereoselective Diels-Alder reaction of naphthoquinone methide 54 with a properly protected unsaturated sugar dienophile 55 (Scheme 1), was proposed as a solution to the task. A simple test of the regioselectivity of the proposed reaction was conducted using model compounds cyanobenzocyclobutene and dihydropyran showed regiospecific formation of the desired adducts 63 and 64. An examination of the structure of the desired sugar dienophile 55 suggested that it could be obtained from D-fucose by a multistep synthesis. A more easily accessible unsaturated sugar derivative 71 is enantiomeric to the desired sugar dienophile 55, except for the terminal methyl group in the latter case being replaced by a hydrogen in the former case. A model Diels-Alder reaction using the sugar dienophile 71 and cyanobenzocyclobutene was undertaken. The desired adducts that formed stereoselectively were isolated and ring opened to form a single compound. The synthetic sequence continued with transketalisation, Swern oxidation, and finally stereoselective hydroxylation to afford the desired model compound 90. Compound 90 was enantiomeric at every carbon to those present in olivin. The preceding work has been the subject matter of a brief communication in the Journal of Organic Chemistry, 45, 1170 (1980). A study was then undertaken to synthesize a model side chain of olivin with the appropriate functionalities and stereochemistry. Diels-Alder reaction of sugar dienophile 125 obtained from D-fucose with benzocyclobutenyl ether 130 was found to be an alternative to the synthetic plan outlined in scheme 1. Two adducts 131 and 132, in a ratio 4:1 were obtained as a result of the above Diels-Alder reaction. Of the two, only adduct 132 showed the desired stereochemistry at its C(,3) center. The stereochemical assignment was based on a comparison of the CD spectra of their elimination products 133 and 134 with that of structurally related 135 whose structure was established using X-ray crystallographic methods. Thus it is concluded that the stereochemistry at C(,3) can be controlled by using a sugar dienophile similar to that of 125, but with a cis-(alpha),(beta)-unsaturated carbonyl system preferably contained in a closed five or six membered ring system. This work is now in progress in the laboratories of Prof. R. W. Franck at Fordham University.
Subject Area
Organic chemistry
Recommended Citation
JOHN, THOMAS VETTATHU, "STUDIES DIRECTED TOWARDS A TOTAL SYNTHESIS OF OLIVIN" (1982). ETD Collection for Fordham University. AAI8213244.
https://research.library.fordham.edu/dissertations/AAI8213244
