text: The lower rim of the cyclooctane B ring containing the first 5 carbon atoms was synthesized in a semisynthesis starting from naturally occurring L-serine (scheme 1). This route started with conversion of the amino group of the serine methyl ester  (1) to the diol ester 2 via diazotization (sodium nitrite/sulfuric acid). After protection of the primary alcohol group to a (t-butyldimethyl) TBS silyl ether (TBSCl / imidazole) and that of the secondary alcohol group with a (Bn) benzyl ether (benzyl imidate, triflic acid),  the  aldehyde 3 was reacted with the methyl ester of isobutyric acid (4) in an Aldol addition to alcohol 5 with 65% stereoselectivity. This group was protected as a PMB (p-methoxybenzyl) ether (again through an imidate) in 6 which enabled organic reduction of the ester to the aldehyde in 7 with DIBAL.
  Completing the cyclooctane ring required 3 more carbon atoms that were supplied by a C2 fragment in an aldol addition and a Grignard C1 fragment (scheme 2). A Mukaiyama aldol addition (magnesium bromide / toluene) took place between aldehyde 7 and ketene silyl acetal 8 with 71% stereoselectivity to alcohol 9 which was protected as the TBS ether 10 (TBSOTf, 2,6-lutidine). The ester group was reduced with DIBAL to an alcohol and then back oxidized to aldehyde 11 by Swern oxidation. Alkylation by methyl magnesium bromide to alcohol 12 and another Swern oxidation gave ketone 13. This group was converted to the silyl enol ether 14 (LHMDS, TMSCl) enabling it to react with NBS to alkyl bromide 15. The C20 methyl group was introduced as methyl iodide in a nucleophilic substitution with a strong base (LHMDS in HMPA) to bromide 16. Then in preparation to ring-closure the TBS ether was deprotected (HCl/THF) to an alcohol which was converted to the aldehyde 17 in a Swern oxidation. The ring-closing reaction was a Reformatskii reaction with Samarium(II) iodide and acetic acid to acetate 18. The stereochemistry of this particular step was of no consequence because the acetate group is dehydrated to the alkene 19 with DBU in benzene.