Asymmetric Total Synthesis and Determination of the Absolute Configuration of (+)-Srilankenyne via Sequence-Sensitive Halogenations Guided by Conformational Analysis

Abstract

This first asymmetric total synthesis of (+)-srilankenyne (1), a halogenated C15 tetrahydropyran acetogenin isolated from Aplysia oculifera, features a sequence-sensitive process guided by conformational analysis to solve the challenging problem of introducing halogens. A competing semipinacol rearrangement during the installation of C(12)-bromide was suppressed by our A1,3 strain-controlled bromination protocol with support from X-ray crystallographic and computational studies. The C(10)-chloride was then placed by the Nakata chloromesylate-mediated chlorination.

Marine natural products

“…The structure of (+)-srilankenyne 1428, previously reported from Aplysia oculifera, was conrmed, and the absolute conguration assigned by asymmetric total synthesis. 607 An elegant stereoselective synthesis, using a one-pot threecomponent bisaldol coupling to set the absolute conguration of seven stereocentres, has afforded a contiguous precursor that undergoes retro-Claisen fragmentation to afford dolabriferol C (seahare, Dolabrifera dolabrifera) under mild conditions. 608 The ease of formation of the MNP from the precursor suggests the isolated metabolite could be an artefact.…”

“…The structure of (+)-srilankenyne 1428 , previously reported from Aplysia oculifera , was confirmed, and the absolute configuration assigned by asymmetric total synthesis. 607 …”

“K‐synthesis”: Recent advancements in natural product synthesis enabled by unique methods and strategies development in Korea

“…The resulting ketoamide compound 54 was then cyclized under dehydrative conditions and subsequently reduced with triethyl silane to yield readily separable diastereomers 55 and 56 (55:56 = 9:1) in 71% yield. 55 was a known precursor to (À)-mesembrane (57). 18 Guncheol Kim and coworkers had also pursued a synthetic program that utilizes Heck reaction as a key transformation for complex natural product synthesis.…”

“…The collaborative researches by the Kim and the Lee groups have been further exemplified by total synthesis of natural products such as macakurzin C ( 170 ), 55 (±)‐decytospolides A ( 171 ) and B ( 172 ), 56 and (+)‐srilankenyne ( 173 , Scheme 11c). 57 …”