2021
DOI: 10.1021/jacsau.1c00178
|View full text |Cite
|
Sign up to set email alerts
|

DFT Study on the Biosynthesis of Verrucosane Diterpenoids and Mangicol Sesterterpenoids: Involvement of Secondary-Carbocation-Free Reaction Cascades

Abstract: Some experimental observations indicate that a sequential formation of secondary (2°) carbocations might be involved in some biosynthetic pathways, including those of verrucosane-type diterpenoids and mangicol-type sesterterpenoids, but it remains controversial whether or not such 2° cations are viable intermediates. Here, we performed comprehensive density functional theory calculations of these biosynthetic pathways. The results do not support previously proposed pathways/mechanisms: in particular, we find t… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2
1
1

Citation Types

1
31
0
2

Year Published

2022
2022
2024
2024

Publication Types

Select...
5
1
1

Relationship

1
6

Authors

Journals

citations
Cited by 23 publications
(34 citation statements)
references
References 64 publications
1
31
0
2
Order By: Relevance
“…AbVS is a bifunctional enzyme with a prenyltransferase (PT) and a terpene cyclase (TC) domain that naturally converts DMAPP and IPP through geranylgeranyl diphosphate (GGPP) into variediene ( 1 , Scheme 1 ). Based on the results from labelling experiments[ 26 , 27 ] and computational studies,[ 28 , 29 ] the reactions from GGPP proceed through 1,11‐10,14 cyclisation to A , followed by Wagner‐Meerwein rearrangement and ring opening to B with a specific stereochemical course that places Me16 in the pro ‐ S and Me17 in the pro ‐ R position. A reverse 14,11 ring closure with simultaneous 2,10 cyclisation leads to C that is the precursor of 1 by deprotonation.…”
Section: Resultsmentioning
confidence: 99%
“…AbVS is a bifunctional enzyme with a prenyltransferase (PT) and a terpene cyclase (TC) domain that naturally converts DMAPP and IPP through geranylgeranyl diphosphate (GGPP) into variediene ( 1 , Scheme 1 ). Based on the results from labelling experiments[ 26 , 27 ] and computational studies,[ 28 , 29 ] the reactions from GGPP proceed through 1,11‐10,14 cyclisation to A , followed by Wagner‐Meerwein rearrangement and ring opening to B with a specific stereochemical course that places Me16 in the pro ‐ S and Me17 in the pro ‐ R position. A reverse 14,11 ring closure with simultaneous 2,10 cyclisation leads to C that is the precursor of 1 by deprotonation.…”
Section: Resultsmentioning
confidence: 99%
“…3,36,37 Finally, homoallylic cations in equilibrium with cyclopropylcarbinyl cations have been described in biosynthetic pathways, where the homoallylic structure is between 2-10 kcal/mol higher in energy than the CPC. 13,15,18,20,22 In investigating this "classical" homoallylic cation, we discovered that C2-C4 bond opening is not the only rearrangement available to CPC cations such as 2a/b. Indeed, a whole number of other rearrangements, which to the best of our knowledge have not been systematically considered before, are actually crucial to the selectivity of these highly substituted CPC cations (Figure 4).…”
Section: Figure 1 Free Energies In Kcal/molmentioning
confidence: 99%
“…2 CPC/BCB cations have since been proposed as intermediates in a variety of organic reactions/rearrangements [3][4][5][6][7][8][9][10][11] and terpene biosynthetic pathways. [12][13][14][15][16][17][18][19][20][21][22] An array of spectroscopic, NMR and computational techniques have been used to probe the C4H7 + system, [23][24][25] which is now understood as an equilibrating mixture of triply-degenerate cyclopropylcarbinyl I and bicyclobutonium II non-classical cations (Figure 1B). These are similar in energy and interconvert stereospecifically through low-energy transition structures (TSs) on a flat potential energy surface (PES).…”
mentioning
confidence: 99%
“…No other class of carbocations has been subjected to more computational investigations than those participating in terpene biosynthesis for their inherent intricacies with unusual rearrangements, multiple competing pathways, post-transition state bifurcations, and flat potential energy surfaces in which intermediates are not minima. 14–27 To address these problems, accurate determination of energy and structure is critical. Furthermore, carbocations provide attractive targets for assessing the performance of theoretical methods for the broad range of features available in their structures, such as strained rings and multiple bonding, and electron delocalization and hyperconjugation in nonclassical cations.…”
Section: Introductionmentioning
confidence: 99%
“…33 Therefore, alternative hGGA functionals such as mPW1PW91 34 by Tantillo's group and M06-2X 35 by Major's, Wu's, and Uchiyama's groups have gained attention. 16–27 An initial benchmark study 36 on carbocations evaluated a few DFAs focusing on hGGAs, including B98, 37 B3LYP, 31,32 BB1K, 38 BMK, 39 mPWB1K 40 and mPW1PW91 34 (Fig. 1).…”
Section: Introductionmentioning
confidence: 99%