Biomimetic Cyclizations of Functionalized Isoprenoid Polyenes: A Cornucopia of Synthetic Opportunities

Abstract

The synthetic aspects of biomimetic cyclizations of isoprenoid polyenes, simulating one of the key steps in the biosynthesis of terpenoids in living organisms, have been reviewed, with emphasis on transformations carried out on carbocyclic systems. These reactions are made possible by a clever choice of initiating and terminating units of cyclization, and by introducing suitable functional groups on the acyclic precursor which can be manipulated after cyclization. Complex functionalized polycyclic structures are thus assembled with an efficiency paralleling or even superior that of purely biochemical processes. In particular, synthetic strategies towards alkyl and hydroxyl-substituted compounds have been examined in detail. The last part of the review has been dedicated to a thorough illustration of carbenium ion initiated polyene cyclizations, with their synthetic applications and a discussion of the different mechanisms proposed.

Biomimetic Cyclization of Geraniol Derivatives, a Useful Tool in the Total Synthesis of Bioactive Monocyclic Terpenoids

“…We explored, therefore, another approach based on the enzymatic kinetic resolution of racemic 10. Indeed, treatment of (±)- 10 These results clearly demonstrate that, in addition to the type of acid catalyst used, apparently small differences in substrate structures dramatically affect the nature of cyclization products.…”

“…The absolute stereochemistry of cyclic products can also be controlled to some extent, either by introducing a directing group on the acyclic precursor, prior to the cyclization, or through alkene enantioface recognition by an external electrophilic species. The interplay between biomimicry and total synthesis was discussed in the past as part of several reviews, including one of the authors [7,10]. In these papers major emphasis was, of course, placed on cyclizations leading to polycyclic terpenoid structures, while simpler cyclizations of geraniol type dienes have not been considered in detail.…”

Carbocations

“…The synthetic aspects of biomimetic cyclizations of isoprenoid polyenes were reviewed. 169 Included was a detailed discussion of carbenium ion-initiated cyclizations, with a discussion of the different mechanisms that have been proposed. A novel biomimetic carbocation polyene cyclization of a daurichromenic ester was reported; an unusual 2 + 2-carbocation cyclization occurred as a side reaction.…”

Lessons and revelations from biomimetic syntheses

“…Indeed, since these seminal reports, the field of biomimetic synthesis has accumulated a rich portfolio of many pivotal experiments and targets, many of which have been reviewed previously [5][6][7][8][9][10] . For example, cascade reactions have been extensively pursued and include studies of steroid and terpenoid synthesis, which used polyene cyclization cascades rather convincingly to mimic the polyene cyclases ( Fig.…”

“…For example, cascade reactions have been extensively pursued and include studies of steroid and terpenoid synthesis, which used polyene cyclization cascades rather convincingly to mimic the polyene cyclases ( Fig. 1c) 6,9,11 . Similarly, reaction cascades are highlighted in the biomimetic synthesis of the endiandric acids 12,13 and in the conversion of squalene-type precursors into members of the Daphniphyllum alkaloid family (Fig.…”