Cyclization of a terpenoid diene with preformed A-B-D rings and its significance for the mechanism of terpenoid terminal epoxide cyclizations

Tamelen, E. E. Van; Lees, R. G.; Grieder, A.

doi:10.1021/ja00814a047

Cited by 12 publications

(5 citation statements)

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“…The acidic character of this residue is enhanced by the neighboring Cys465 and Cys533 with which it interacts through two hydrogen bonds. The second stage of the mechanism was initially thought to involve the sequential formation of the four rings (named A–D) in a concerted manner. − Corey et al proposed that the formation of the A-ring should be concomitant with the protonation of the epoxide, in a concerted SN2 substitution-like process. This proposal was confirmed very recently by QM/MM calculations .…”

Section: Enzymes Involved In the Cholesterol Pathwaymentioning

confidence: 99%

Cholesterol Biosynthesis: A Mechanistic Overview

et al. 2016

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Cholesterol is an essential component of cell membranes and the precursor for the synthesis of steroid hormones and bile acids. The synthesis of this molecule occurs partially in a membranous world (especially the last steps), where the enzymes, substrates, and products involved tend to be extremely hydrophobic. The importance of cholesterol has increased in the past half-century because of its association with cardiovascular diseases, which are considered one of the leading causes of death worldwide. In light of the current need for new drugs capable of controlling the levels of cholesterol in the bloodstream, it is important to understand how cholesterol is synthesized in the organism and identify the main enzymes involved in this process. Taking this into account, this review presents a detailed description of several enzymes involved in the biosynthesis of cholesterol. In this regard, the structure and catalytic mechanism of the enzymes involved in cholesterol biosynthesis, from the initial two-carbon acetyl-CoA building block, will be reviewed and their current pharmacological importance discussed. We believe that this review may contribute to a deeper level of understanding of cholesterol metabolism and that it will serve as a useful resource for future studies of the cholesterol biosynthesis pathway.

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Section: Enzymes Involved In the Cholesterol Pathwaymentioning

confidence: 99%

Cholesterol Biosynthesis: A Mechanistic Overview

et al. 2016

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“…2), yields the indenyl carbocation 7. The cation 7 is then easily converted to the final carbocation product 2 via subsequent low-energy barrier hydrogen migrations already reported experimentally by van Tamelen et al [15]. The calculated energy barrier for the ring expansion process 6 3 7 via the transition state structure TS7 is for ϳ20 kcal/mol lower than the calculated barrier for the 1,4-hydride shift 3 3 6.…”

Section: Resultsmentioning

confidence: 55%

DFT study of rearrangements in cyclopentylheptenyl carbocations

Vrček

2006

Int J of Quantum Chemistry

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Carbocation rearrangements relevant to sterol biosynthesis were investigated computationally by using the model cyclopentylheptenyl carbocations 1A and 1B. Five different rearrangement pathways of these equilibrating cations were located at the potential energy surface (PES), all calculated at the B3LYP/6-31G(d) level of theory. Each of these five distinct pathways differs from previous mechanistic proposals, and each involves new and unusual intermediates.

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“…One of the original postulates laid down in the application of the biogenetic isoprene rule to triterpene biogenesis isthat such multi-step schemes be assumed to proceed uninterrupted to the end product (i. e., termination steps are irreversible) (3)(4)(5). This "non-stop" hypothesis has been verified in triterpene biosynthesis by the absence of tritium loss (25)(26)(27)(28) and, albeit negative evidence, in the non-incorporation of various conceivable alcohol intermediates (29)(30)(31).…”

Section: A Introductionmentioning

confidence: 90%

“…A mechanistic variant of the biogenetic isoprene rule is the "X-group" hypothesis in which one or more stabilized intermediates are postulated during propagation (34). Although the possibility that the "X-group" could be hydroxyl has been considered, as mentioned above, attempts to realize the further conversion of several hypothetical alcohol intermediates in terpene biosynthesis have been uniformly unsuccessful (29)(30)(31)36). However, other nucleophiles (e. g., phosphate) or a strategically-placed nucleophilic site on the enzyme surface could serve as the "X-group".…”

Section: A Introductionmentioning

confidence: 99%