Scalable Asymmetric Total Syntheses of (+)-Psoracorylifol B and (+)-ent-Psoracorylifol C

Abstract

The first, asymmetric total syntheses of potent antimicrobial Psoracorylifol B (>1.3 g obtained, dr 10.5:1) with a 9.4% overall yield on a gram scale in 14 steps and ent-Psoracorylifol C with a 4.3% yield in 16 steps were achieved. The key features of our synthesis include (i) sequential, rarely explored Achmatowicz rearrangement/bicycloketalization to construct the 6,8-dioxabicyclo[3.2.1]octane core, and (ii) Cu-mediated SN2' methylation or Johnson-Claisen rearrangement to stereoselectively install the all-carbon quaternary stereocenter. This concise, highly efficient, and scalable synthetic route may provide expedited and practical access to psoracorylifols and their analogues for further biological activity evaluation.

Furan Oxidation Reactions in the Total Synthesis of Natural Products

“…The obtained product 352 was then converted into (+)-psoracorylifol B (353) (Scheme 86). 134 In 2015, from the ciliate microorganism Spirostorum teres, Iio et al isolated the defense toxins, diastereomeric spirostomins A (357) and B (358), determined their struc-tures and synthesized them from furan and 4,7-dimethyl-5-siloxy-α-tetralone 354. The addition of 2-furyllithium to tetralone 354 produced a diastereomeric mixture of 1-(2furyl)tetralin-1-ols 355 and 356.…”

Advances in the Asymmetric Synthesis of Bridged and Fused Bicyclic Acetals

“…The Achmatowicz rearrangement-bicyclo acetalization strategy was used by Tong and his group [51] Intramolecular acetalization/RCM represented an efficient and interesting synthetic strategy employed for several syntheses of bicyclic acetals. A beautiful illustration was exemplified by Burke and co-workers [52] through a publication on an efficient acetalization/ring closing metathesis strategy for the synthesis of potentially rigid bicyclic acetal and acetal systems of sialic acid derivatives KDN, a potential oncofetal antigen, and N-acetylneuraminic acid (Neu5Ac An application of the Burke's protocol was observed in the total synthesis of (+)-exo-brevicomin.…”

Achmatowicz reaction and its application in the syntheses of bioactive molecules

“…108-113 This alternative furylcarbinol ring expansion was nicely employed in natural product total syntheses. 114-117 …”

“…In particular, the development of highly effective methods for transforming the Achmatowicz reaction products, namely the resulting functionalized dihydropyranone acetals, has provided the possibility of accessing a wide variety of key pyran-based substructures. These include Kishi reduction, 144 Feringa-O'Doherty O-glycosylation, 81, 145, 146 [5+2] cycloaddition, 147, 148 and more recently, spyroketalization, 114 reductive ring expansion, 149 and trans- selective arylation. 150 These are among the most common transformations applied to the Achmatowicz reaction products.…”

“…Tong and co-workers reported asymmetric total syntheses of PsB ( 101 ) and PsC exploiting an Achmatowicz reaction on the furan intermediate 105 followed by bicycloketalization for construction of the 6,8-DOBCO substructure in 104. 114 …”