Swapan Majumdar

Axially Chiral Binaphthyl Surrogates with an Inner N-H-N Hydrogen Bond

Novel chiral binaphtyl surrogates with an inner hydrogen bond have been created. The NH appears at 13.0-13.3 ppm in thier (1)H NMR spectrum, indicating extremely strong hydrogen bonding. Enantiomers of these compounds were stable at ambient temperature and separable by HPLC with a chiral stationary phase. The half-lives of racemization of the enantiomer are in the range 3 months to 2 years at 20 degrees C, and the barriers for racemization are in the range 27.0 to 28.2 kcal/mol. An X-ray crystal analysis of the compound (R = CHPh(2)) shows that the pseudonaphthyl skeleton including CN...HN is almost completely planar and the dihedral angle between the pseudonaphthalene and naphthalene rings is 128 degrees .

Proprotein Convertase Inhibitory Activities of Flavonoids Isolated from Oroxylum Indicum

BACKGROUND Proprotein Convertases (PCs) or Proprotein Convertase Subtilisin/Kexins (PCSKs) belong to a family of calcium-dependent endoproteases that are structurally related to bacterial subtilisin and yeast kexin. These enzymes play major roles in the processing of inactive precursor proteins producing their bioactive mature forms that are implicated in a wide variety of diseases including cancer, viral and bacterial infections. As a result, PCs are major targets for intervention of these diseases. OBJECTIVE Our objective in this study is to find non-peptide inhibitors of PC-enzymes from a potential natural source. RESULTS Herein we describe several natural flavonoid compounds as inhibitors of PC-enzymes including furin, a key member. These compounds were isolated from the medicinal plant Oroxylum indicum, fully characterized and tested in vitro for their PC-inhibitory property against the fluorogenic peptide substrate, Boc-RVRR-MCA (Boc = tert-butyloxy carbonyl, MCA = 4-methyl coumarin7-amide). The measured Ki and IC50 were found to be in low microM ranges. A comparative analysis of inhibition against furin, PC4, PC5 and PC7 suggested a partial selectivity towards PC4. These flavonoids also blocked efficiently the PC4-mediated processing of a fluorogenic peptide derived from the processing site of its substrate, pro-Insulin Growth Factor-1 (proIGF-1). This anti-protease activity may provide a rationale for the observed anticancer and anti-HIV properties of some of these flavonoid compounds. This is the first demonstration of anti-PC activity of flavonoid compounds.

General solvent-free highly selective N-tert-butyloxycarbonylation strategy using protic ionic liquid as an efficient catalyst

A simple, rapid and solvent-free protocol is described for the chemo-selective transformation of amines to tert-butyloxycarbonyl protected derivatives (NHBoc) using Boc2O and imidazolium trifluoroacetate protic ionic liquid (5–20 mol%). Unwanted side products such as isocyanate, urea or N,N-di-Boc were not detected. The scope of the protection strategy was successfully explored for substrate alcohols, phenols and thiol at elevated temperatures. Optically pure amino acids, amino acid esters and amino alcohols were efficiently converted to the corresponding N-Boc protected derivatives in excellent yields without racemization at the chiral center. The distinct advantages of this method are: operational simplicity, cleaner reaction, high selectivity, excellent yield, rapid reaction convergence, easy preparation and recyclability of the catalyst.

Expeditious synthesis of chiral six and seven membered nitrogen heterocycles from carbohydrate amines by N-allyl carbohydrate nitrone cycloaddition: Tuning of regioselectivity by N-substitution

Abstract The cycloaddition of N -allyl carbohydrate nitrones leads to enantiomerically pure six and seven membered nitrogen heterocycles and the regioselectivity of the cycloaddition can be tuned by changing the substituent on the nitrogen atom.

Grindstone chemistry: protic ionic liquid-substrate tuned green synthesis of 1,2-disubstituted and 2-substituted benzimidazoles with outstanding selectivity

An environmentally benign and highly catalyst-substrate controlled synthesis of 1,2-disubstituted and 2-substituted benzimidazoles with outstanding selectivity has been developed through grinding a mixture of o-phenylenediamines, suitable aldehydes and an imidazolium trifluoroacetate protic ionic liquid catalyst. The newly developed metal-free catalysis approach produced 1,2-disubstituted benzimidazoles from aromatic aldehydes bearing electron donating group, whereas aromatic aldehydes possessing electron withdrawing groups and aldehydes with 2-alkoxy substitution selectively furnished 2-substituted benzimidazoles and their chiral analogues. Low energy consumption, short reaction time and solvent-free synthesis make this methodology green, providing a useful contribution to the existing procedures available for the synthesis of benzimidazole derivatives.

Regioselective synthesis of chiral six- and seven-membered N-heterocycles from N-allyl carbohydrate nitrones: Tuning of regioselectivity by N-substitution

Abstract The intramolecular cycloaddition of N-allyl carbohydrate nitrones leads to enantiomerically pure six- and seven-membered nitrogen heterocycles and the regioselectivity of the cycloaddition was controlled by changing the substituent on the nitrogen atom of the N-allyl moiety.

Insights into the origins of configurational stability of axially chiral biaryl amines with an intramolecular N-H-N hydrogen bond.

Configurationally stable chiral biaryl amines with an intramolecular N-H-N hydrogen bond have been developed. The barriers for racemization are in the range of 19.3-28.2 kcal/mol, which corresponds to the half-lives of racemization of the enantiomers in the range of 7 s to 2 years at 20 degrees C. Enantiomers of some of these compounds were separable by HPLC with chiral stationary phases. The biaryl amines are supposed to have a conformation similar to that of a binaphthyl skeleton, which was indicated by an X-ray crystal analysis of a biaryl amine. The N-H appears at 11.1-13.3 ppm in their (1)H NMR spectrum in CDCl(3), indicating strong hydrogen bonding. Biaryl amines with an extremely strong intramolecular N-H-N hydrogen bond (delta(NH) approximately 13 ppm) were assumed to undergo racemization without cleavage of an N-H-N hydrogen bond, while those with a mediumly strong N-H-N hydrogen bond (delta(NH) approximately 11 ppm) are assumed to undergo racemization via cleavage of an N-H-N hydrogen bond. Hydrogen/deuterium exchange of a chiral biaryl amine was found to proceed without any trace of racemization.

Activation of 1,3-dioxolane by a protic ionic liquid in aqueous media: a green strategy for the selective hydrolytic cleavage of acetals and ketals

A convenient method for the deprotection of acetals and ketals was achieved using an imidazolium based protic ionic liquid as a catalyst in aqueous medium via the dual activation of dioxolane. The protocol is highly efficient towards the deprotection of acyclic and cyclic acetals, ketals, benzylidene acetals and tetrahydropyranyl (THP) ethers, giving excellent yields. Functional groups such as tert-butyl ester, tert-butyl dimethyl silyl (TBDMS), N-tert-butyloxycarbonyl (N-Boc), and double bond, mesyl, nitro, and glycosidic linkage were tolerated under the benign reaction conditions. Selective deprotection of the 5,6-isopropylidene moiety in 1,2:5,6-di-O-isopropylidene hexose and 3,5-cyclohexylidene moiety in pentose derivatives proceeded smoothly without affecting the 1,2-protected group. The attractive features of this new protocol are the use of mild reaction conditions, tolerance of a wide range of functional groups, use of relatively non-toxic solvent systems and recyclability of the ionic liquid catalyst.

Dynamic cell patterning of photoresponsive hyaluronic acid hydrogels.

Techniques to pattern cells on biocompatible hydrogels allow for the creation of highly controlled cell microenvironments within materials that mimic the physicochemical properties of native tissues. Such technology has the potential to further enhance our knowledge of cell biology and to play a role in the development of novel tissue engineering devices. Light is an ideal stimulus to catalyze pattern formation since it can be controlled spatially as well as temporally. Herein, we have developed and enhanced a hydrogel cell patterning strategy. It is based on photoactive caged RGDS peptides incorporated into a hyaluronic acid (HA) hydrogel, which can be subsequently activated with near-UV light to create cell-adhesive regions within an otherwise non-adhesive hydrogel. With this strategy, we have been able to pattern multiple cell populations-either in contact with one another or held apart-on an underlying chemically patterned HA hydrogel. Furthermore, the hydrogel cell pattern could be altered with time, even 2 weeks after initial seeding, to create additional adhesive regions to regulate the direction of cell growth and migration. These dynamic hydrogel cell patterns, created with a standard fluorescence microscope, were shown to be robust and lasted at least 3 weeks in vitro.

Synthesis of Chiral 10, 11 and 12-Membered Nitrogen and Oxygen Heterocycles by Intramolecular Nitrile Oxide Cycloaddition of Tethered N- and O-Allyl Carbohydrate Derivatives

Abstract Chiral 10 to 12-membered nitrogen and oxygen heterocycles fused to isoxazoline rings have been prepared in a highly regioselective and stereoselective manner by intramolecular nitrile oxide cycloaddition of tethered N- and O-allyl carbohydrate derivatives. The use of a –Y–Ar-CH2 tether containing a 1,2-disubstituted aromatic ring between the heteroatom attached to the nitrile oxide-bearing carbohydrate scaffold, and the allyl group, facilitates the formation of the medium-sized rings. The cycloaddition afforded bridged isoxazolines in the cases of O-tethered allyl carbohydrate derivatives, whereas a fused isoxazoline resulted when a N(Ts)-tethered allyl derivative was used.