scholarly journals Mechanism Underlying Anti-Markovnikov Addition in the Reaction of Pentalenene Synthase

Biochemistry ◽  
2020 ◽  
Vol 59 (35) ◽  
pp. 3271-3283
Author(s):  
Jason O. Matos ◽  
Ramasamy P. Kumar ◽  
Alison C. Ma ◽  
MacKenzie Patterson ◽  
Isaac J. Krauss ◽  
...  
Keyword(s):  
Pentalenene Synthase ◽  
Markovnikov Addition

scholarly journals Mechanism Underlying Anti-Markovnikov Addition in the Reaction of Pentalenene Synthase

2020 ◽  
Author(s):  
Jason O. Matos ◽  
Ramasamy P. Kumar ◽  
Alison C. Ma ◽  
MacKenzie Patterson ◽  
Isaac J. Krauss ◽  
...  
Keyword(s):  
Positive Charge ◽  
High Energy ◽  
Terpene Synthase ◽  
Side Chain ◽  
Aromatic Side Chain ◽  
Terpene Synthases ◽  
In The Wild ◽  
Pentalenene Synthase ◽  
Markovnikov Addition ◽  
Secondary Carbon

AbstractMost terpene synthase reactions follow Markovnikov rules for formation of high energy carbenium ion intermediates. However, there are notable exceptions. For example, pentalenene synthase (PS) undergoes an initial anti-Markovnikov cyclization reaction followed by a 1,2-hydride shift to form an intermediate humulyl cation with positive charge on the secondary carbon C9 of the farnesyl diphosphate substrate. The mechanism by which these enzymes stabilize and guide regioselectivity of secondary carbocations has not heretofore been elucidated. In an effort to better understand these reactions, we grew crystals of apo-PS, soaked them with the non-reactive substrate analog 12,13-difluorofarnesyl diphosphate, and solved the x-ray structure of the resulting complex at 2.2 Å resolution. The most striking feature of the active site structure is that C9 is positioned 3.5 Å above the center of the side chain benzene ring of residue F76, perfectly poised for stabilization of the charge through a cation-π interaction. In addition, the main chain carbonyl of I177 and neighboring intramolecular C6,C7-double bond are positioned to stabilize the carbocation by interaction with the face opposite that of F76. Mutagenesis experiments also support a role for residue 76 in cation-π interactions. Most interesting is the F76W mutant which gives a mixture of products that likely result from stabilizing a positive charge on the adjacent secondary carbon C10 in addition to C9 as in the wild-type enzyme. The crystal structure of the F76W mutant clearly shows carbons C9 and C10 centered above the fused benzene and pyrrole rings of the indole side chain, respectively, such that a carbocation at either position could be stabilized in this complex, and two anti-Markovnikov products, pentalenene and humulene, are formed. Finally, we show that there is a rough correlation (although not absolute) of an aromatic side chain (F or Y) at position 76 in related terpene synthases from Streptomyces that catalyze similar anti-Markovnikov addition reactions.

Harnessing Applied Potential: The Anti-Markovnikov Hydrocarboxylation of Substituted Olefins

2019 ◽  
Author(s):  
Anas Alkayal ◽  
Volodymyr Tabas ◽  
Andrei V. Malkov ◽  
Benjamin Buckley
Keyword(s):  
Carboxylic Acid ◽  
Applied Potential ◽  
Markovnikov Addition

<div>The construction of carboxylic acid compounds in a selective fashion, from low value materials such as alkenes remains a long-standing challenge to synthetic chemists. In particular, anti-Markovnikov addition to styrenes are underdeveloped. Herein we report a new electrosynthetic approach to the selective hydrocarboxylation of substituted alkenes.</div>

Harnessing Applied Potential: The Anti-Markovnikov Hydrocarboxylation of Substituted Olefins

2019 ◽  
Author(s):  
Anas Alkayal ◽  
Volodymyr Tabas ◽  
Andrei V. Malkov ◽  
Benjamin Buckley
Keyword(s):  
Carboxylic Acid ◽  
Applied Potential ◽  
Markovnikov Addition

<div>The construction of carboxylic acid compounds in a selective fashion, from low value materials such as alkenes remains a long-standing challenge to synthetic chemists. In particular, anti-Markovnikov addition to styrenes are underdeveloped. Herein we report a new electrosynthetic approach to the selective hydrocarboxylation of substituted alkenes.</div>

Rhodium-Catalyzed Selectiveanti-Markovnikov Addition of Carboxylic Acids to Alkynes

2010 ◽  
Vol 12 (23) ◽  
pp. 5498-5501 ◽  
Author(s):  
Alexandre Lumbroso ◽  
Nicolas R. Vautravers ◽  
Bernhard Breit
Keyword(s):  
Carboxylic Acids ◽  
Markovnikov Addition

Three-component reaction between secondary phosphine sulfides, elemental selenium and vinyl ethers: the first examples of Markovnikov addition of thioselenophosphinic acids to double bond

Tetrahedron ◽  
2013 ◽  
Vol 69 (30) ◽  
pp. 6185-6195 ◽  
Author(s):  
Ludmila A. Oparina ◽  
Alexander V. Artem'ev ◽  
Oksana V. Vysotskaya ◽  
Nikita A. Kolyvanov ◽  
Irina Yu. Bagryanskaya ◽  
...  
Keyword(s):  
Double Bond ◽  
Elemental Selenium ◽  
Secondary Phosphine ◽  
Vinyl Ethers ◽  
Three Component Reaction ◽  
Markovnikov Addition

Synthesis and Characterization of β-Haloalkenyl-λ3-bromanes:  Stereoselective Markovnikov Addition of Difluoro(aryl)-λ3-bromane to Terminal Acetylenes

2005 ◽  
Vol 127 (30) ◽  
pp. 10460-10461 ◽  
Author(s):  
Masahito Ochiai ◽  
Yoshio Nishi ◽  
Takeshi Mori ◽  
Norihiro Tada ◽  
Takashi Suefuji ◽  
...  
Keyword(s):  
Synthesis And Characterization ◽  
Terminal Acetylenes ◽  
Markovnikov Addition

Anti-Markovnikov Addition of Thiols Across Double Bonds Catalyzed by H-Rho-Zeolite

Synlett ◽  
1999 ◽  
Vol 1999 (12) ◽  
pp. 1921-1922 ◽  
Author(s):  
Pradeep Kumar ◽  
Rajesh Kumar Pandey ◽  
Vishnumurthy R. Hegde
Keyword(s):  
Double Bonds ◽  
Markovnikov Addition
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