Suvratha Krishnamurthy

Epoxy amino acids produced from allylglycines intramolecularly cyclised to yield four stereoisomers of 4-hydroxyproline derivatives

Derivatives of 2-amino-4-pentenoic acid (allylglycine) were efficiently resolved using Subtilisin or acylase. The side-chain unsaturated bond of the enantiomerically pure amino acid with tert-butoxycarbonyl (Boc) protection was smoothly epoxidized with m-chloroperbenzoic acid. When the Boc protection of the amino group was removed, the amino group intramolecularly attacked the side-chain epoxide, generating compounds with five-membered rings: the 4-hydroxyproline derivatives. Two diastereomeric products were formed through the cyclisation reaction, for example, (2S,4S)-4-hydroxyproline benzyl ester (cis-8) and (2S,4R)-4-hydroxyproline benzyl ester (trans-8) were formed from (2S)-amino acid with a side-chain epoxide. Compound (2S,4S)-4-hydroxyproline benzyl ester (cis-8) was transformed to a lactone (cis-hydroxyproline lactone, 10) with the removal of benzyl alcohol. The cis-conformation was essential for the intramolecular ester exchange reaction; in fact, no lactone formation was observed for the trans isomer (trans-8). The separation of cis-hydroxyproline lactone and the trans-isomeric hydroxyproline benzyl ester was facile and clear, in contrast to the difficult separation of cis- and trans-hydroxyproline derivatives. Thus, two diastereomers of hydroxyproline derivatives for L-hydroxyproline and also for D-hydroxyproline were obtained, i.e., four diastereomers of hydroxyproline derivatives.

Synthesis of Novel Spiro[indol-2,2′-pyrroles] Using Isocyanide-Based Multicomponent Reaction

Abstract An efficient and facile method for the synthesis of novel spiro[indole-2,2′-pyrroles] from N-methyl-3-isatin imines, t-butyl isocyanide, and dialkyl acetylenedicarboxylate has been achieved by [3 + 2] cyclo addition reaction. All the products were purified by column chromatography as yellow solids and confirmed with 1H NMR, 13C NMR, fast atom bombardment, mass, and infrared. Compound 11 was further confirmed with x-ray analysis. GRAPHICAL ABSTRACT

One-pot four component synthesis of novel 3-furyl coumarin derivatives

AbstractEfficient and facile synthesis of 3-furyl coumarin derivatives have been achieved by reaction of 4-chloro-3-formylcoumarin, secondary amines, dialkyl acetylenedicarboxylates and diversely substituted isocyanides using four component, one-pot reaction. All the products were isolated as yellow color fluorescent solids by column chromatography in quantitative yield and characterized with 1H NMR, 13C NMR, IR and FAB mass. Graphical AbstractSynthesis of 3-furyl coumarin derivatives have been achieved by reaction of 4-chloro-3-formylcoumarin, secondary amines, dialkyl acetylenedicarboxylates and diversely substituted isocyanides using four component, one-pot reaction.

Efficient synthesis of novel pyrrolo[2,3-c]pyridone derivatives using the Ugi four-component reaction followed by condensation reaction

An efficient, mild and multicomponent synthesis of novel heterocyclic compounds possessing the pyrrolo[2,3-c]pyridone backbone was achieved using the Ugi four-component reaction and post-condensation of the Ugi adduct. This method offers many advantages, such as an easy handling procedure, atom economy, short reaction time, and a huge molecular library that can be synthesized by changing the substituents on the four independent starting materials. This methodology was also successfully employed for the electron deficient anilines and phenyl glyoxylic acids having CF3 group. All the products were characterized using NMR (1H and 13C) spectroscopy and FAB mass spectrometry. Product 6g was further characterized by X-ray diffraction analysis.

α-Chymotrypsin and L-acylase aided synthesis of 5-hydroxypipecolic acid via Jacobsen's hydrolytic kinetic resolution of epoxy amino acids

Diethyl malonate derivatives were used to synthesize racemic 2-amino-5-hexenoic acid. These racemic 2-amino-5-hexenoic acid (homoallylyglycine) derivatives were efficiently resolved aided by α-chymotrypsin or L-acylase, giving rise to L- and D-enantiomers. These isolated enantiomerically pure amino acids with tert-butoxycarbonyl (Boc) protection were oxidised with 3-chloroperbenzoic acid. The oxidation gave rise to inseparable diastereomeric epoxides due to a newly generated chiral center at the C5 carbon. The isolation of one of the diastereomeric epoxides was possible by selectively converting the remaining diastereomer into a dihydroxyl compound catalysed by Jacobsens hydrolytic kinetic resolution (HKR). The isolated epoxide was regioselectively attacked by LiBr to give vicinal halohydrin, with bromide attacking the terminal C6 carbon. Boc deprotection of the halohydrin led to intramolecular cyclization by attack of free amine at the C6 carbon, generating a single isomer of 5-hydroxypipecolic acid which was effortlessly recovered in good yield after re-protection of the amine with the Boc group. Similarly the dihydroxyl compound isolated earlier was converted to a halohydrin with iodine at the C6 carbon. This was feasible by efficient regioselective mono-tosylation with catalytic Bu2SnO followed by iodine substitution. This was utilized to synthesize the 5-hydroxypipecolic acid derivative in the same described sequence consisting of Boc removal by acid treatment, cyclization, reprotection and purification. Finally the same sequence was repeated with the D-isomer and two diastereomers were isolated.

Crystal structure of ethyl 2-(2-{1-[N-(4-bromo-phen-yl)-2-oxo-2-phenyl-acetamido]-2-tert-butyl-amino-2-oxo-ethyl}-1H-pyrrol-1-yl)acetate.

In the title compound, C28H30BrN3O5, there is an intramolecular N—H⋯O hydrogen bond and an intramolecular C—H⋯O hydrogen bond, both forming S(9) ring motifs. The planes of the 4-bromophenyl ring and the phenyl ring are inclined to that of the pyrrole ring by 48.05 (12) and 77.45 (14)°, respectively, and to one another by 56.25 (12)°. In the crystal, molecules are linked via C—H⋯O hydrogen bonds and C—H⋯π interactions, forming slabs parallel to (10-1).

Synthesis and Molecular Structure of tert-Butyl 3-oxo-2-oxa-5-azabicyclo[2.2.2]octane-5-carboxylate

The compound tert-butyl 3-oxo-2-oxa-5-azabicyclo[2.2.2]octane-5-carboxylate was synthesized as a cyclic amino acid ester from the corresponding ethyl 2-amino-4-(2-oxiranyl)butanoate HCl salt via an intramolecular lactonization reaction and was characterized by using 1H NMR spectroscopy and high-resolution mass spectrometry. The product was then recrystallized from dichloromethane/diethyl ether and its structure was determined via single crystal X-ray diffraction analysis. The crystal was found to be of the monoclinic space group P21/c (no. 14) with  A,  A,  A, β = 114.186(13)°, and = 1.350 g/cm3 at 123 K. The compound has bicyclo[2.2.2]octane structure including a lactone moiety and a piperidine ring, and the two diastereomers of the molecules are present in a 1 : 1 ratio in the crystal.

Crystal structure of benzyl 3-oxo-2-oxa-5-aza-bicyclo-[2.2.1]heptane-5-carboxyl-ate.

The title compound, C13H13NO4 (also known as N-benzyloxycarbonyl-4-hydroxy-l-proline lactone), crystallizes with two molecules in the asymmetric unit. They have slightly different conformations: the fused ring systems almost overlap, but different C—O—C—C torsion angles for the central chains of −155.5 (2) and −178.6 (2)° lead to different twists for the terminal benzene ring. In the crystal, the molecules are linked by C—H⋯O interactions, generating a three-dimensional network. The absolute structure was established based on an unchanging chiral centre in the synthesis.

Crystal structure of 3,4-dimethyl 2-(tert-butyl­amino)-5-[2-oxo-4-(thio­morpholin-4-yl)-2H-chromen-3-yl]furan-3,4-di­carboxyl­ate ethyl acetate hemisolvate

In the title hemisolvate, C25H28N2O7S·0.5C4H8O2, the thiomorpholine ring adopts a chair conformation, with the exocyclic N—C bond in an equatorial orientation. The dihedral angle between the coumarin ring system (r.m.s. deviation = 0.044 Å) and the furan ring is 64.84 (6)°. An intramolecular N—H⋯O hydrogen bond closes an S(6) ring. The ethyl acetate solvent molecule is disordered about a crystallographic inversion centre. In the crystal, the components are linked by C—H⋯O and C—H⋯S hydrogen bonds, generating a three-dimensional network.

Crystal structure of (tert-butyl­carbamo­yl)(4-chloro-2-oxo-2H-chromen-3-yl)methyl acetate

In the title compound, C17H18ClNO5, which was synthesized by reacting 4-chloro-3-formylcoumarin, acetic acid and tert-butyl isocyanide, the acetamido side chain is convoluted with ring-to-side chain C—C—C—C, C—C—C—N and C—C—N—C torsion angles of −123.30 (14), −135.73 (12) and 176.10 (12)°, respectively. In the crystal, N—H⋯O and weak C—H⋯O hydrogen bonds are present, which together with π–π coumarin-ring interactions [ring centroid separations = 3.4582 (8) and 3.6421 (9) Å], give rise to a layered structure lying parallel to (001).