Synthesis of the C1-C16 fragment of bryostatin for incorporation into 20,20-fluorinated analogues

The stereoselective synthesis of a carboxylic acid ester corresponding to the C1 -C16 fragment of bryostatin, with 4-methoxybenzyl (PMB) protection for the 7-hydroxyl group, is reported. The key steps included a Horner-Wadsworth-Emmons reaction between (5R)-3-[ (E)-2-tri- isop ropyls ilyloxy ethylidene]-6-(4-methoxybenzyloxy)-5-triethylsilyloxyhexanal and dimethyl (4,5,6R,85)-10-hydroxy-6,8-di-O-isopropylidene 4 (4 methoxybenzyloxy)-3,3-dimethyl-2-oxodecan-1-yl phosphonate, that gave the corresponding (E)-alkene, followed by selective cleavage of the triethylsilyl ether and cyclisation to give the required 2,6-cis-disubstituted 4-[(Z)-tri-isopropylsilyloxyethylide]tetrahydropyran. Oxidation of the primary alcohol gave the corresponding carboxylic acid that was converted into the required allyl ester. (C) 2020 Elsevier Ltd. All rights reserved.

Automated summary

The stereoselective synthesis of a carboxylic acid ester corresponding to the C1 -C16 fragment of bryostatin was successfully achieved through key steps including reactions and oxidation.