A General Route toward the Synthesis of the Cladiellin Skeleton Utilizing a SmI₂-Mediated Cyclization

Abstract

An efficient synthesis of the cladiellin skeleton is reported utilizing methods that were previously developed in this laboratory. The approach is based on a SmI(2)-mediated cyclization reaction for the construction of the oxacyclononane unit. A [4 + 3] annulation strategy was used to create the octahydroisobenzofuran moiety. This route provides the cladiellin skeleton in only 14 steps without the use of protecting groups. The present approach also enabled the synthesis of the 3,7-diastereomer of the natural product polyanthellin A.

Efficient Total Synthesis of Bioactive Natural Products: A Personal Record

“…Using a similar strategy for the introduction of the A/B ring system prior to construction of the medium‐sized C ring, Campbell and Johnson applied a Lewis acid catalyzed [3 + 2] cycloaddition reaction to provide stereoselective access to the A/B ring fragment in their total synthesis of (+)‐polyanthellin A [52]. In contrast, Molander et al [53]. completed the total synthesis of deacetoxyalcyonin acetate via the photochemical rearrangement of a cyclobutanone.…”

Efficient synthesis of 8-oxa-bicyclo[3.2.1]octane derivatives from d-arabinose

“…7 Two strategies are available for the construction of 8-oxabicyclo[3.2.1]octane derivatives. One is to create the cyclic systems in one step employing reactions such as [4+3] cycloaddition, 3,8 oxidopyrylium [5+2] cycloaddition, 4,6 and Prins-Pinacol reaction. 2 Another is to create the cyclic systems by stepwise processes, including SmI 2 -mediated nucleophilic acyl addition 9 and intramolecular oxymercuration.…”

Collective Synthesis of Cladiellins Based on the Gold‐Catalyzed Cascade Reaction of 1,7‐Diynes

“…[5] Despite these reports, the antitumor and antimicrobial activities of the many other compounds belonging to the cladiellin family have not been extensively evaluated. [7][8][9][10][11][12][13][14][15] In fact, research into the total synthesis of cladiellins has played an important role in determining their structures. [6] Several members of the cladiellin family have been successfully synthesized by a number of research groups.…”

“…[6] Several members of the cladiellin family have been successfully synthesized by a number of research groups. [7][8][9][10][11][12][13][14][15] In fact, research into the total synthesis of cladiellins has played an important role in determining their structures. [7, 8, 9e] The tricyclic compound 10 has been used as a common latestage intermediate in a number synthetic strategies for accessing various cladiellins, including 1, 2, 5, and 6.…”