Total Synthesis of Calystegine B₄

Abstract

The total synthesis of calystegine B4 was achieved in 10 steps from (–)‐D‐lyxose by using a new synthetic strategy to obtain the requisite protected hydroxylated 4‐aminocyclohept‐2‐en‐1‐one without the problem of regioisomer formation that was a problem in the earlier synthesis of this natural product. The key steps included a Petasis–borono‐Mannich reaction and a ring‐closing metathesis reaction.

Reactivity and Synthetic Applications of Multicomponent Petasis Reactions

“…Pyne and coworkers reported the PR-based synthesis of diverse polyhydroxylated alkaloids, 197 among which was a 10-step total synthesis of calystegine B4 alkaloids. 198 Different from a previous zinc-mediated tandem reaction with a RCM–hydroboration–oxidation sequence, 199 a PR of benzylamine, ( E )-styrylboronic acid, and (−)- d -lyxose was used for the synthesis of aminotetrol 285 , which was converted to the RCM substrate 286 to give oxidation–RCM or RCM–oxidation product 287 , and the remaining steps of deprotection and cyclization gave calystegine B4 288 with an overall yield of 3.4 or 4.7% (Scheme 75). This study exemplifies the synthesis of calystegine alkaloids starting from monosaccharides.…”

“…Pyne and coworkers reported various synthetic studies for the synthesis of polyhydroxylated monocyclic alkaloids as well as their application as starting materials to access more complex alkaloids. ,,,− Polyhydroxylated pyrrolidine alkaloids dihydroxymethyl–dihydroxypyrrolidine (DMDP) 307 and 1,4-dideoxy-1,4-imino- d -arabinitol (DAB) 308 were found in diverse plant species. Bouillon and Pyne reported a synthesis of DMDP and DAB from l -xylose over seven and eight steps with an overall yield of 35 and 22%, respectively.…”

“…Pyne and coworkers reported the PR-based synthesis of diverse polyhydroxylated alkaloids, 197 among which was a 10-step total synthesis of calystegine B4 alkaloids. 198 Different from a previous zinc-mediated tandem reaction with a RCM− hydroboration−oxidation sequence, 199 ). This study exemplifies the synthesis of calystegine alkaloids starting from monosaccharides.…”

“…This study exemplifies the synthesis of calystegine alkaloids starting from monosaccharides. 198 Conduramine oligomers, aminocyclohexenetriols in which an amino group is present, are common fragments included in several natural products. The synthesis of conduramines has been achieved via different approaches.…”

New Frontiers on Human Safe Insecticides and Fungicides: An Opinion on Trehalase Inhibitors

“…Among the three calystegines shown in Figure 4, calystegine B4 (23) was more effective towards pig kidney trehalase than towards rat intestinal trehalase (IC50 = 4.8 μM vs IC50 = 9.8 μM) and showed competitive inhibition with a Ki value of 1.2 μM. There are very few total syntheses of calystegine B4, which is due to the structural complexity of this compound [61][62][63]. Pyrrolizidines are bicyclic iminosugars bearing two fused pyrrolidine rings and a bridgehead nitrogen atom.…”