Esterification/RCM strategy

Having completed the synthesis of 13-demethyllyngbyaloside B (5), we were now in a position to tackle the parent natural product, lyngbyaloside B (1). Our initial synthesis plan for 1 followed that of 5, basically relying on the esterification/RCM strategy for the construction of the macrocyclic skeleton (Scheme 7). Thus, it was conceived that the macrolactone 36 would be available from the tertiary alcohol 37 and the carboxylic acids 9a,b. 

Jennings strategy for obtaining the macrolide skeleton was Yamaguchi esterification and ring closing metathesis (RCM) with 175 and 176 (Scheme 36). Construction of the key 2,6-cis-tetrahydropyran in 176 was carried out via diastereoselective axial reduction of an oxonium cation. The precursor, a pyranone, was prepared via RCM of divinyl ester 177. An asymmetric center was made by Brown s asymmetric allylation. 

Our scheme of a-pyrone synthesis involves the esterification of homoallylic alcohols with acryloyl chloride, followed by ring-closing metathesis (RCM) using Grubbs ruthenium catalyst (Scheme 6) (44). We have identified a large number of such pyrone-containing natural products that can be readily synthesized via our allylboration strategy. Representative examples of our syntheses are described below. 

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