Palladium-Catalyzed Synthesis of Novel Optically Active Tryptophan Analogues

Abstract

[reaction: see text] Both unsaturated proline derivatives and optically active tryptophan analogues have been obtained via Pd-catalyzed cyclization of aniline-containing acetylenic amino acids. The side chain length of the cyclization precursor determines which one of the two possible products will be formed.

Recent Advances in the Synthesis of Unnatural α-Amino Acids

“…The synthesis starts from the appropriate 2,4-or 2,3-disubstituted phenylhydrazines 36 and optically active N,N-diprotected Lglutamic -aldehyde 35, and it utilizes Fischer-indole synthesis as a key step affording the mixture of mono-Boc/di-Boc tryptophan esters (37 and 38). 6 , the sultam auxiliary was removed by treatment with LiOH in THF/H 2 O solution to afford the corresponding free allylglycine derivatives (48)(49)(50)(51) without any loss of stereochemical purity (Scheme 8). Unlike most of the previously reported methods that required a multi-step stereoselective synthesis, this method enables the generation of optically active ring-A Fig.…”

“…The initially formed tertiary iminium ion 145 was trapped by the hydride donor to give proline derivatives 146 and 147 as a 9(S) : 1(R) mixture of diastereoisomers [48,49] (Scheme 23). The starting material can easily be synthesized from racemic 2-amino-4-pentynoic ester 141 via a Sonogashira-type coupling with iodobenzene, affording 142.…”

Pd-Catalysed Synthesis of 5-Substituted Proline Derivatives from Acetylene-Containing Amino Acids

“…This result is markedly different from our earlier reported results, in which a similar Boc-protected compound did not show any cyclisation. 7 Furthermore, subjection of the substituted aniline 9, obtained in 91% yield starting from 2-amino-4-pentynoic acid derivative 4, to the aforementioned catalyst in refluxing acetonitrile also led to the rapid formation of cyclic enamide 10 in 57% yield. Surprisingly, exposure of 9 to the same conditions at room temperature gave rise to the formation of 10 in 51% yield after prolonged reaction times of over several days, but, in that case, formation of the corresponding ketone was not observed.…”

Transition Metal‐Catalyzed Synthesis of Novel Biologically Relevant Tryptophan Analogues

“…[9] Of these potentially biologically relevant a-amino acids, only isotryptophan (9) itself has been previously prepared in optically active form. In that preparation, [10] the synthesis proceeded via a copper-mediated cyclization [11] of an ortho-ethynylaniline moiety that was connected to a Schˆllkopf chiral auxiliary.…”