Concise Synthesis of 9,11-Secosteroids Pinnigorgiols B and E

Abstract

Pinnigorgiols B and E are 9,11-secosteroids with a unique tricyclic γ-diketone framework. Herein, we report the first synthesis of these natural products from inexpensive, commercially available ergosterol. This synthesis features a semipinacol rearrangement and an acyl radical cyclization/hemiketalization cascade; the latter efficiently assembled the tricyclic γ-diketone skeleton, with two rings and three contiguous stereogenic centers being formed in a single step.

Marine natural products

“…A biosynthesis-inspired synthesis of pinnigorgiols B and E has been reported, with the methodology incorporating an elegant acyl radical cyclisation/hemiketalisation cascade that formed two rings and three contiguous stereogenic centres in one step. 593 Genome mining of the branching stony coral Acropora millepora identied a predicted protein sequence AmAMP1 that shared some resemblance to known coral and jellysh antimicrobial peptides and for which homologues could be identied in a range of other corals. 594 The mature peptide contains six cysteine residues making it related to the Shk group of sea anemone neurotoxins.…”

“…A biosynthesis-inspired synthesis of pinnigorgiols B and E has been reported, with the methodology incorporating an elegant acyl radical cyclisation/hemiketalisation cascade that formed two rings and three contiguous stereogenic centres in one step. 593…”

Biogenetic space-guided synthesis of rearranged terpenoids

“…We chose to highlight the approach by Gui and co-workers, as it is an impressive example of a semisynthesis taking into consideration the (hypothetical) biogenesis. 56 A biosynthetic proposal by Kigoshi and Kita envisioned an a-ketol rearrangement taking place in co-isolated pinnisterol E (92) to yield a-hydroxy ketone 93, which then could react in a second, this time vinylogous a-ketol rearrangement, to yield the key diketone 94 (Scheme 14). As diketone 94 should be transformed into the natural product under acidic catalysis, Gui defined 94 as a key intermediate to their approach.…”

Recent development and applications of semipinacol rearrangement reactions

“…Inspired by a proposed biosynthetic α-ketol rearrangement cascade, Gui and coworkers ingeniously accomplished a concise synthesis of pinnigorgiols B and E from an inexpensive steroid. 76 As depicted in Scheme 20 , dehydroergosterol 102 was converted to mesylate 103 in 5 steps. Subsequent semipinacol rearrangement of 103 under basic conditions would afford ketone 104 with the conversion of the trans -bicyclo[4.4.0]decane to the cis -bicyclo[5.3.0]decane ring system.…”