A stereocontrolled enantiospecific route to tirandamycin B

Abstract

The enal 15 was synthesized in enantiomerically pure form starting from (S)-3-benzyloxy-2-methylpropanol 3 via highly regio-and stereo-selective methylation of the +epoxy acrylate 5 with trimethylaluminium in the presence of water, developing an enantiospecific route to tirandamycin B.

Total Synthesis of (−)-Tirandamycin C

“…Many methods involving asymmetric aldol or crotylboration reactions of highly enantioenriched aldehyde substrates fail to provide synthetically useful selectivities for the desired anti,anti -stereotriads. Consequently, multistep, indirect methods have been employed to access this stereotriad unit. , …”

“…Treatment of phosphonate 6 with KO t -Bu in THF followed by addition of aldehyde 5 gave N- dimethoxybenzyl (DMB) protected tirandamycin C ( 23 ) in 74% yield. Finally, deprotection of 23 by treatment with TFA provided synthetic (−)-tirandamycin C ( 1 ) in 31% yield (64% based on recovered starting material). The spectroscopic data ( 1 H NMR, 13 C NMR, [α] D ) of synthetic (−)-tirandamycin C were in excellent agreement with the data previously reported for the natural product …”

Recent Advances in the Total Synthesis of Tetramic Acid-Containing Natural Products

“…Obviously, the racemic tetramic acid fragment 33 could be easily accessed by subjecting phosphonate 31 to glycine methyl ester to provide the amide 32 that further proceeded with a typical Lacey-Dieckmann cyclization and a DMB protection (Schlessinger et al had prepared similar tetramic acid core via the same method in his synthesis of tirandamycin A; see [48]) [49]. In contrast, the bicyclic ketal fragment 36 asks for precautious design to achieve the desired stereochemistry presented in tirandamycin C [25,48,[50][51][52][53][54][55][56]. The starting homoallylic alcohol 34, prepared from the mismatched double asymmetric stannylcrotylboration of an aldehyde, was treated with excess MeLi at low temperature to trigger the formation of the lactol intermediate C.…”

The Achmatowicz Rearrangement – Oxidative Ring Expansion of Furfuryl Alcohols

“…[50][51][52][53][54][55] In particular, the in situ ketalization in the oxidative ring enlargement of di-or polyhydroxylated furans, pioneered by Martin, 27 has attracted much attention and found application in numerous total synthetic scenarios. [56][57][58][59][60][61][62][63][64] In this regard, Tong and coworkers most recently published an elegant route towards the bicyclo[3.2.1]octane framework of the psoracorylifol family (Scheme 17). 65 In combination with the Sharpless asymmetric dihydroxylation to yield the enantiopure diol, the m-chloroperbenzoic acid induced formation of the bicyclic ketal served as a scalable and reliable procedure to access the important synthetic intermediate.…”