Lakshminarasimhan Damodharan

First and unexpected synthesis of macrocyclic cyclophane-based unusual α-amino acid derivatives by phosphazene base without high dilution conditions

First synthesis of a macrocylic cyclophane-based unusual alpha-amino acid derivative 11 by coupling of ethyl isocyanoacetate with 1,2-bis(4-bromomethylphenyl)ethane under phase-transfer catalysis (PTC) conditions. Phosphazene base such as 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP) is useful to improve the yield of cyclophane derivative without high dilution conditions.

Conformational Preferences of Heterochiral Peptides. Crystal Structures of Heterochiral Peptides Boc-(D) Val-(D) Ala-Leu-Ala-OMe and Boc-Val-Ala-Leu-(D) Ala-OMe-Enhanced Stability of β-sheet Through C-H…O Hydrogen Bonds

Abstract The crystal structures of Boc-(D) Val-(D) Ala-Leu-Ala-OMe (vaLA) and Boc-Val-Ala-Leu-(D) Ala-OMe (VALa) have been determined. vaLA crystallises in space group P212121 with a = 9.401 (4), b = 17.253 (5), c = 36.276 (9)Å, V = 5884 (3) Å3, Z = 8, R = 0.086. VALa crystallises in space group P21 with a = 9.683 (9), b = 17.355 (7), c = 18.187 (9) Å, β = 95.84 (8)°, V = 3040(4) Å3, Z = 4, R = 0.125. There are two molecules in the asymmetric unit in antiparallel β-sheet arrangement in both the structures. Several of the Cα hydrogens are in hydrogen bonding contact with the carbonyl oxygen in the adjacent strand. An analysis of the observed conformational feature of D-chiral amino acid residues in oligopeptides, using coordinates of 123 crystal structures selected from the 1998 release of CSD has been carried out. This shows that all the residues except D-isoleucine prefer both extended and αL conformation though the frequence of occurence may not be equal. In addition to this, D-leucine, valine, proline and phenylalanine have assumed αR conformations in solid state. D-leucine has a strong preference for helical conformation in linear peptides whereas they prefer an extended conformation in cyclic peptides.

Solvent interactions with β-Cyclodextrin as observed in crystal structures

Nimesulide, an anti-inflammatory drug, was complexed with β cyclodextrin (βCD) in the presence of lysine in 10:10:1 molar ratio to increase its water solubility. The complexation did not take place in the crystal structure, but it exhibits two different crystal forms. The crystal structures show a difference in hydration pattern and conservation of the organic molecule 2,4 methyl pentane diol (MPD) binding site. Molecular mechanics studies carried out suggest a probable mode of binding of nimesulide with βCD.

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

The title compounds, C(19)H(19)I(2)NO(3) and C(19)H(19)Br(2)NO(3), are derivatives of alpha-aminoisobutyric acid with halogen substituents at the para and meta positions, respectively. The ethoxycarbonyl and formamide side chains attached to the C(alpha) atom of the molecule adopt extended and folded conformations, respectively. The crystal structures are stabilized by N-H.O, C-H.O, C-Br.O and C-I.O interactions.

Synthesis of two new hexaquinanes: advanced C20 precursors to dodecahedrane

A simple synthesis of hexaquinane diones 2 and 22 involving bench-top chemicals is reported. These two hexaquinanes are advanced C20 precursors to dodecahedrane 1 either by CC bond formation reactions or by the isomerisation approach.

Ethyl 6-acetylamino-6,7-dihydro-5H-dibenzo[a,c]cycloheptene-6-carboxylate

The title compound, C(20)H(21)NO(3), is a derivative of Aib (alpha-aminoisobutyric acid) and is cyclized at the C(alpha) position by biphenyl rings. The seven-membered ring possesses C2 symmetry. The C(alpha) cyclization causes the backbone to assume a helical conformation in the crystal structure. The packing of the molecules is stabilized by intermolecular C-H.O, C-H.pi and N-H.O hydrogen bonds.

Conformational switching caused by bi­phenyl substitution at the Cα position: ethyl 2‐benzyl‐2‐(formyl­amino)‐3‐phenyl­propionate and ethyl 3‐(1,1′‐bi­phenyl‐4‐yl)‐2‐(formyl­amino)‐2‐(4‐phenyl­benzyl)­propionate

The title compounds, C19H21NO3 and C31H29NO3, are derivatives of alpha-aminoisobutyric acid, with benzyl and dibenzyl substitution. The pseudo-peptide formed by the N-formyl and ethyl ester substitution at the Calpha position switches from a trans-trans to a trans-cis configuration as a result of biphenyl substitution. The packing of the compounds is stabilized by N-H...O and C-H...O hydrogen bonds.