Synthesis and Stereochemical Assignments ofcis- andtrans-1-Amino- 4-ethylcyclohexa-2,5-diene as Models for Amiclenomycin

Abstract

As an approach to the synthesis of amiclenomycin (1), we describe here the synthesis of a 1-aminocyclohexa-2,5-diene moiety. The cis isomer 2 was obtained by means of a Diels− Alder reaction between trans-1,2-bis(phenylsulfonyl)ethylene and N-(allyloxycarbonyl)hexa-1,3-diene (13), followed by reductive elimination of the phenylsulfinyl groups. To obtain the trans isomer 3, O-(trimethylsilyl)hexa-1,3-diene (16) was used. This afforded the cis-hydroxylated Diels−Alder adducts 18, which were transformed into the corresponding

Inhibition of Diamino Pelargonic Acid Aminotransferase, an Enzyme of the Biotin Biosynthetic Pathway, by Amiclenomycin: A Mechanistic Study

“…The X-ray structure reveals, as expected, the presence of an adduct between ACM and PLP that is bound noncovalently to the protein. Coordinates are consistent with the postulated aromatic adduct 2, although it is not straightforward, at that resolution, to differentiate an aromatic ring from a cyclohexa-2,5-diene (like intermediate i in Scheme 2), which is expected to be planar [9]. We present here definitive proof of the adduct×s structure based on mass spectrometry data.…”

“…To obtain the compound and also to eliminate the stereochemical ambiguity, we achieved the synthesis of both cis-and trans-isomers, 1a and 1b, respectively [20], and we concluded that the natural product was indeed the cis-isomer. In the course of this study, two other pairs of cis-and trans-aminocyclohexadienes, 3a,b [20] and 4a,b [9], were obtained and investigated as inhibitors.…”

Synthesis of a Model Compound of Corydendramine A via a Julia Coupling

“…[7] After protection with a tert-butoxycarbamate group, the N-Bocpiperidine-2-methanol 4 was converted to the carbaldehyde 5 [8] by using a Swern oxidation. [9] The synthesis of the lipophilic tail (Scheme 2) began with trans, trans-2,6-nonadienal 6 and use of a Horner-Wadsworth-Emmons [10] reaction to afford the ethyl ester 7. This ester was subsequently reduced [11] with 2.2 equivalents of diisobutyl aluminum hydride (DIBAL-H) in toluene to afford the alcohol 8 after workup.…”

Inhibition of 7,8-diaminopelargonic acid aminotransferase by amiclenomycin and analogues

“…Total synthesis of this unusual amino acid was necessary because the natural compound was no longer available and because we speculated that the trans configuration proposed by Okami et al [1] was ambiguous and needed confirmation. We thus undertook the synthesis of cis-and trans-amiclenomycin (1a and 1b) using two unequivocal routes (Scheme 2) [6,7]. As shown below, we obtained cis-and trans-amiclenomycin and analogues, and unambiguously assigned the cis configuration to the natural antibiotic, in contrast with the assignment tentatively proposed by Okami.…”

“…The inactivation by amiclenomycin 1a and cis-analogues resisted prolonged dialysis, a common criterion for irreversible inactivation. Complete kinetic characterization was Scheme 2 Outline of the synthesis of amiclenomycin, its trans stereoisomer and derivatives P and P refer to protecting groups [6,7].…”