I am looking at Compound A (see below) and am trying to figure out a decarboxylation mechanism that results in Compound B (see below). I have come up with an internal mechanism that might work that I have attached to this question. However, I am trying to connect it to enzyme catalysis, and I am thinking that a PLP-dependent enzyme is involved I just cannot quite figure out the mechanism.
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2 Answers
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A PLP-dependent enzyme could certainly accomplish a reaction like this. An example of something similar is the PLP-dependent enzyme KAPA synthase in the biotin biosynthesis pathway. In that reaction, alanine is decarboxylated and a new bond is formed between the alpha carbon and an electrophilic thioester. Interestingly, the proposed mechanism involves deprotonation of the alpha carbon rather than decarboxylation as the initial step. Only after the new C-C bond is formed is the carboxylate lost:
1: Source: Webster, S.P, et al. (1998) Characterisation of S-amino-7-oxononanoate synthase: A bacterial PLP-dependent, acyl CoA condensing enzyme. Biochemical Society Transactions 26(3):S268. DOI: 10.1042/bst026s268
Although this is an intermolecular reaction, your proposed intramolecular reaction should be even easier to accomplish. An example of a PLP-dependent enzyme catalyzed reaction that results in intramolecular cyclization (but not decarboxylation) is that of aminocyclopropane carboxylate synthase.
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One thing you do not want to propose is an unstabilized carbanion, either enzymatically or non-enzymatically, as the nucleophile in this $\ce{S_N2^'}$ cyclization. @Andrew has demonstrated how pyridoxal phosphate (PLP) can provide stabilized anionic character at the desired carbon site followed by acylation or, in this instance, cyclization with subsequent decarboxylation. Upon examining your structures, I suspected that this reaction may have been part of a biosynthetic study on the formation of ergot alkaloids.
Kozikowski, et. al.[1] synthesized racemic amino acids 1a and 1b to determine if one of the enantiomers was capable of incorporation into the ergot skeleton via the agency of Claviceps sp. strain SD58. A doped sample of 1a/1b produced elymoclavine 5 that displayed molecular ions for M and M+3. The presumed pathway involves dehydration of 1 to diene 2, which is ostensibly oxidized to vinyl epoxide 3 with cytochrome P-450. Decarboxylative cyclization proceeds to give (E)-allylic alcohol 4, chanoclavine-I. The (Z)-allylic alcohol of 4, isochanoclavine-I, has been proposed[2] to form by isomerization of (E)-4 or may form directly from vinyl epoxide depending on the conformation of the epoxide during the cyclization. These latter two points are significant because it is known[2] that the carbon of the hydroxymethyl group of 4 becomes $\ce{C7}$ in elymoclavine 5.
- A. P. Kozikowski and J-P. Wu, M. Shibuya and H. G. Floss, J. Am. Chem. Soc., 1988, 110, 1970-1971. https://doi.org/10.1021/ja00214a054
- H. G. Floss, Tetrahedron, 1976, 32, 873-912. https://doi.org/10.1016/0040-4020(76)85047-8
