Synthesis of Indan-Based Unusual α-Amino Acid Derivatives under Phase-Transfer Catalysis Conditions

Abstract

Conformationally constrained cyclic alpha-amino acid derivatives were synthesized under solid-liquid phase-transfer catalysis conditions. This methodology involves the bis-alkylation of ethyl isocyanoacetate with various alpha,alpha'-dibromo-o-xylene derivatives [alpha,alpha'-dibromo-o-xylene 5, 2,3-bis(bromomethyl)-1, 4-dimethoxybenzene 6, 1,2-bis(bromomethyl)-4,5-dibromobenzene 7, 2, 3-bis(bromomethyl)naphthalene 8, 1,8-bis(bromomethyl)-naphthalene 9, 6,7-bis(bromomethyl)-2,2-dimethyl-1H-phenalene-1,3(2H)-dione 10, 2, 3-bis(bromomethyl)-1,4-anthraquinone 11, 6, 7-bis(bromomethyl)quinoxaline 12, 3,4-bis(bromomethyl)furan 13, 1,2, 4,5-tetrakis(bromomethyl)benzene 28, and hexakis(bromomethyl)benzene 30] using potassium carbonate as a base and tetrabutylammonium hydrogensulfate as a phase-transfer catalyst to give corresponding isonitrile derivatives, which upon hydrolysis with HCl in ethanol gave amino esters. Using this method electron-deficient as well as electron-rich and halogen-substituted indan-based alpha-amino acids were prepared. The preparation of bis-indan as well as tris-indan alpha-amino esters is also described.

Synthesis of the four stereoisomers of cyclobutane analogues of phenylalanine in enantiomerically pure form

“…The double alkylation of ethyl isocyanoacetate with 1,3-dibromo-1-phenylpropane, under conditions reported in the literature, 21 gave a mixture of at least four compounds from which trans-isocyanide rac-16 and cis-isocyanide rac-17 could be isolated by column chromatography in 6% and 50% yield, respectively (Scheme 5). The relative stereochemistries of the isocyanate esters rac-16 and rac-17 were assigned on the basis of 1 H NMR spectroscopy.…”

“…Several amino acids, 21 among them 1-aminocyclobutanecarboxylic acid, 14 have been synthesized starting from ethyl isocyanoacetate. The main advantage of this starting material is that the nitrogen atom is already attached to Ca, meaning that a rearrangement reaction would not be necessary.…”

Ethyl 2-formamido-2-(4-iodobenzyl)-3-(4-iodophenyl)propionate and ethyl 2-(3-bromobenzyl)-3-(3-bromophenyl)-2-formamidopropionate

“…Compound (I) was synthesized under phase-transfer conditions (PTC) using ethyl isocyanoacetate as a glycine equivalent (see reaction Scheme below) in a four-step sequence starting from p-toluidine (Kotha & Brahmachary, 1997. Thus, diazotization of compound (1) and subsequent iodination of the diazo derivative with KI gave 4-iodotoluene, (2).…”

Expanding the Diversity of Polycyclic Aromatics Through a Suzuki–Miyaura Cross‐Coupling Strategy

“…[45] When the C-terminal Phe residue in the chemotactic agent www.eurjoc.orgHCO-Met-Leu-Phe-OH (FMLP) was replaced by Ind, the resulting modified analogue was shown to be highly active in superoxide production. Mash and co-workers have designed ladder-like molecules displaying intricate hydrogenbonding patterns based on Ind precursors.…”