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.