Revisiting sesquiterpene biosynthetic pathways leading to santalene and its analogues: A comprehensive mechanistic study
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India. .Organic & Biomolecular Chemistry (Impact Factor: 3.56). 09/2012; 10(39):7996-8006. DOI: 10.1039/c2ob26027a
Santalene and bergamotene are the major olefinic sesquiterpenes responsible for the fragrance of sandalwood oil. Herein we report the details of density functional theory investigations on the biosynthetic pathway of this important class of terpenes. The mechanistic study has been found to be effective toward gaining significant new insight into different possibilities for the formation of the key intermediates involved in santalene and bergamotene biosynthesis. The stereoelectronic features of the transition states and intermediates for (i) ring closure of the initial bisabolyl cation, and (ii) skeletal rearrangements in the ensuing bicyclic carbocationic intermediates leading to (-)-epi-β-santalene, (-)-β-santalene, (-)-α-santalene, (+)-epi-β-santalene, exo-β-bergamotene, endo-β-bergamotene, exo-α-bergamotene, and endo-α-bergamotene are presented. Interesting structural features pertaining to certain new carbocationic intermediates (such as ) resulting from the ring closure of bisabolyl cation are discussed. Extensive conformational sampling of all key intermediates along the biosynthetic pathway offered new insight into the role of the isoprenyl side chain conformation in the formation of santalene and its analogues. Although the major bicyclic products in Santalum album appear to arise from the right or left handed helical form of farnesyl pyrophosphate (FPP), different alternatives for their formation are found to be energetically feasible. The interconversion of the exo and endo isomers of bisabolyl cation and a likely epimerization, both with interesting mechanistic implications, are presented. The exo to endo conversion is identified to be energetically more favorable than another pathway emanating from the left handed helical FPP. The role of pyrophosphate (OPP(-)) in the penultimate deprotonation step leading to olefinic sesquiterpenes is also examined.
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ABSTRACT: One of the leading goals in contemporary chemical catalysis is to render improved efficiency to existing catalytic protocols. A few pertinent trends can readily be noticed from the current literature encompassing both catalysis development and applications. First, there has been an unprecedented growth in the use of metal-free organocatalytic methods toward realizing a plethora of synthetic targets. In parallel, the availability of newer and more efficient transition metal catalytic methods for the synthesis of complex molecules has become a reality over the years. The most recent developments indicate the emergence of multicatalytic approaches under one-pot reaction conditions, wherein the complementary attributes of two or more catalysts are made to work together. This domain, known as cooperative catalysis, is showing signs of immense promise. The mechanistic underpinnings of both of these forms of catalysis have been investigated by using a range of computational chemistry tools. With the availability of improved accuracy in computational methods aided by ever increasing computing technologies, the exploration of potential energy surfaces relating to complex cooperative catalytic systems has become more affordable. In this review, we have chosen a select set of examples from the emerging domain of cooperative catalysis to illustrate how computational methods have been effectively used toward gaining vital molecular insights. Emphasis is placed on mechanistic details, energetics of reaction, and, more importantly, on transition states that are responsible for stereoselectivity in asymmetric cooperative catalytic reactions.Keywords: organocatalysis; transition metal catalysis; cooperative catalysis; counterion; noncovalent interaction; stereoselectivity; density functional theory (DFT); transition state modeling
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