Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400076, India.
Org Biomol Chem. 2012 Oct 21;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 b) 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.
檀香烯和佛手烯是负责檀香油香气的主要烯烃倍半萜烯。本文报道了密度泛函理论对这一重要萜烯类生物合成途径的详细研究。该机理研究对于深入了解檀香烯和佛手烯生物合成中关键中间体形成的不同可能性具有重要意义。本文还介绍了（i）初始倍半蒈基阳离子的环闭，以及（ii）随后的双环碳阳离子中间体中骨架重排，从而导致（-）-表-β-檀香烯、（-）-β-檀香烯、（-）-α-檀香烯、（+）-表-β-檀香烯、外-β-佛手烯、内-β-佛手烯、外-α-佛手烯和内-α-佛手烯等关键中间体的立体电子特征。讨论了涉及某些新碳阳离子中间体（如 b）的某些有趣的结构特征，这些中间体是由倍半蒈基阳离子的环闭形成的。对生物合成途径中所有关键中间体的广泛构象采样提供了对异戊烯基侧链构象在檀香烯及其类似物形成中的作用的新见解。尽管 Santalum album 中的主要双环产物似乎来自法呢基焦磷酸（FPP）的右手或左手螺旋形式，但发现其形成的不同替代方案在能量上是可行的。还提出了外消旋体和顺式异构体的互变以及可能的差向异构化，这两者都具有有趣的机理意义。外消旋体到内消旋体的转化被确定为比源自左手螺旋 FPP 的另一种途径更有利。焦磷酸（OPP(-)）在导致烯烃倍半萜烯的最后一步脱质子化中的作用也进行了研究。
