Synthesis of the C9–C25 Subunit of Spirastrellolide B

Abstract

The synthesis of the C9–C25 subunit of the marine natural product spirastrellolide B is reported. The key synthetic features included the union of the two key fragments 5 and 6 via a Suzuki–Miyaura coupling reaction and a late-stage, one-pot sequential deprotection/cascade Achmatowicz rearrangement–spiroketalization to install the key spirocyclic intermediate present in the C9–C25 fragment of spirastrellolide B. The synthesis of the C9–C16 fragment 6 was accomplished via a phosphate tether mediated ring-closing metathesis (RCM), a subsequent hydroboration–oxidation protocol, followed by other stereoselective transformations in a facile manner. The spirocyclic intermediate was further functionalized utilizing a Lindlar/NaBH4 reduction protocol to furnish the C9–C25 subunit 3.

Current Applications of Suzuki–Miyaura Coupling Reaction in The Total Synthesis of Natural Products: An update

“…The important synthetic segment 396 was provided in moderate yield (50%) via the SMCR of furan substrate 389 with the 1,3‐diol‐containing synthon 388 in the presence of Pd(PPh 3 ) 4 and K 3 PO 4 . Spirastrellolide B 386 was obtained in several steps from compound 390 in acceptable yield (Scheme ) …”

“…The synthesis of the C9‐C25 subunit of the marine naturally occurring compound Spirastrellolide B 386 was achieved and reported . The key synthetic steps comprise the combination of the two key segments of 388 and 389 via a SMCR followed by sequential deprotected/cascade.…”

“…[206] The synthesis of the C9-C25 subunit of the marine naturally occurring compound Spirastrellolide B 386 was achieved and reported. [207] The key synthetic steps comprise the combination of the two key segments of 388 and 389 via a SMCR followed by sequential deprotected/ cascade. Achmatowicz rearrangement-spiroketalization in one pot fashion to assemble the key spirocyclic intermediate present in the C9-C25 segment of Spirastrellolide B. Spirastrellolide A was the first member of the Spirastrellolide family being isolated by Andersen et al from the extracts of the Caribbean marine sponge Spirastrella coccinea in 2003.…”

“…Spirastrellolide B 386 was obtained in several steps from compound 390 in acceptable yield (Scheme 66). [207] The ajudazols, 391 and 392 obtained from the myxobacterium Chondromyces crocatus, [211] are placed in the class of polyketides with unique framework and attractive biological activities such as selective inhibitory activities of the mitochondrial respiratory chain. [212] The key structural moeity in these compounds is a fully functionalized hydroxyl-isochromanone core.…”

P-Tether-Mediated, Iterative SN2′-Cuprate Alkylation Strategy to Skipped Polyol Stereotetrads: Utility of an Oxidative “Function Switch” with Phosphite–Borane Tethers

“…Over the past decade, our group has focused on the development of phosphate triester tether-mediated methods for the two-directional synthesis of complex polyols from C 2 -symmetric dienediol substrates. 1 These methods have served as key transformations in a number of total and formal syntheses, 2 and on-going efforts continue to exploit the inherent chemistry of bicyclic phosphate triesters—particularly their ability to mediate multiple transformations in one-pot sequential processes—in the two-directional synthesis of complex polyols. 3 Much like the synthetic community at large, we seek intriguing targets containing interesting chemical fragments to help catalyze method development and expansion.…”