Biosynthetically Inspired Syntheses of Secu′amamine A and Fluvirosaones A and B

Abstract

Presented here is a concise synthesis of secu′amamine A, and fluvirosaones A and B from readily available allosecurinine and viroallosecurinine. The key C2‐enamine derivative of (viro)allosecurinine, the presumed biosynthetic precursors of these natural products, was accessed, for the first time, by a VO(acac)2‐mediated regioselective Polonovski reaction. Formal hydration and 1,2‐amine shift of this pluripotent enamine compound afforded secu′amamine A. Formal oxidative [3+2] cycloaddition reaction between this enamine and TMS‐substituted methallyl iodide reagent paved the way to the precursors of fluvirosaones A and B. The relative stereochemistry at the C2 position of these advanced intermediates governs the fate of 1,2‐amine shift leading to fluvirosaones A and B. The syntheses of potential biosynthetic precursors and investigations of their chemical reactivities have provided insights regarding the biogenesis of these natural products.

The Chemistry of High‐Oxidation State Securinega Alkaloids

“…Consistent with the original proposal by Magnus [23] and the synthetic verification by us, [24] C3‐alcohol derivative 167 is the plausible biosynthetic precursor of secu'amamine A ( 24 ). It is likely that (3 S )‐3‐hydroxyallosecurinine ( 138 ), a potential natural product yet to be discovered, undergoes a 1,2‐amine shift for the biosynthesis of secu'amamine A ( 24 ).…”

“…For the biosynthesis of fluvirosaones A ( 4 ) and B ( 28 ), we propose that enamine 166 undergoes a stereodivergent formal [3+2] cycloaddition reaction with an external three‐carbon unit. Our synthetic studies showed that the configuration at C2 determines the fate of 1,2‐amine shift in that 2‐ epi ‐fluvirosaone A ( 148 ) undergoes immediate rearrangement to fluvirosaone B ( 28 ) [24] . We postulate that an analogous stereodivergent biosynthetic process is operative in vivo .…”

“…Members in this group show distinct structural diversities compared to other groups. Secu'amamines A ( 24 ) [21] and H ( 25 ) [22] consist of a unique azabicyclo‐[3.3.1]‐nonane core structure presumably generated by a 1,2‐amine shift via aziridinium ion intermediate (Figure 5A) [23,24] . Another structurally fascinating feature displayed in this group of high‐oxidation state securinega alkaloids is the presence of diverse carbon units assembled via different connection modes at C3.…”

“…Recently, we completed the biosynthetically inspired synthesis of (−)‐secu'amamine A ( 24 ) and fluvirosaones A ( 4 ) and B ( 28 ) [24] . The crux of our successful synthesis was an efficient and selective access to the C2‐enamine derivative of (viro)allosecurinine (Scheme 12).…”

“…Our synthesis of naturally occurring (+)‐fluvirosaones A ( 4 ) and B ( 28 ) commenced with the total synthesis of viroallosecurinine based on Peixoto's report [46] with modifications during the resolution process [24] . Viroallosecurinine was then transformed to its C2‐enamine derivative (+)‐ 136 by employing our oxidation/VO(acac) 2 ‐based protocol.…”