Vommina V. Suresh Babu

Supramolecular Helical Fluid Columns from Self‐Assembly of Homomeric Dipeptides

Herein, we demonstrate that with the widespread theme of residue patterning and stereochemical restraints of self-complimenting proteinogenic amino acids, a new and rich class of homomeric dipeptides exhibiting two-dimensional fluid aggregates with hierarchical ordering can be obtained. In particular, a simple way of achieving a class of functional dipeptides, wherein the first and the second residues chosen are L-/D-alanines and L-/D-leucines, has been accomplished. The supramolecules synthesized can be regarded as intermediates between polycatenars and taper-shaped amphiphiles because they possess two lipophilic segments interlinked by a peptide unit (spacer). Two pairs of enantiomers and their respective diastereomers derived from these amino acids are evidenced to self-organize into a helical columnar phase through hydrogen bonding by means of FTIR, UV/Vis, and chiroptical circular dichroism (CD) spectral analyses as well as by optical, calorimetric, electrical switching, and X-ray studies. The CD and X-ray studies have revealed that the form chirality (handedness) and the magnitude of out-of-plane fluctuations of the lattice planes of the fluid supramolecular columnar structures are solely directed by the stereochemistry encoded in the spacer. Of special significance, the less frequently found oblique helical columnar phase formed by a pair of enantiomers derived from L-/D-alanines, unlike those derived from other amino acids, exhibit ferroelectric behavior; the measured spontaneous polarization is as high as 440 nC cm(-2). Besides, all these supramolecules form stable organogels in ethanol and the CD and SEM studies on a representative gel suggest the presence of helical structures.

SYNTHESIS OF PEPTIDES EMPLOYING FMOC-AMINO ACID CHLORIDES AND COMMERCIAL ZINC DUST

Abstract Coupling of Fmoc-amino acid chlorides mediated by activated commercial zinc dust for the synthesis of peptides is described. The reaction is carried out in an organic medium. The necessity of using an inorganic base like NaHCO 3 Na 2 CO 3 or an organic base like DIEA/NMM/TEA/pyridine is circumvented. The coupling is reasonably fast, clean, racemization free and high yielding.

(Fluoren-9-ylmethoxy)carbonyl (Fmoc) amino acid azides: Synthesis, isolation, characterisation, stability and application to synthesis of peptides

The synthesis of Fmoc amino acid azides starting from the corresponding protected amino acid and sodium azide (NaN3) by the mixed anhydride method using isobutoxycarbonyl chloride (IBC-Cl) or by the acid chloride method is described. Isolated as crystalline solids, they are stable at room temperature, with a long shelf-life, as well as in aqueous washing operations. They are useful as coupling agents in peptide synthesis.

Rapid and efficient synthesis of peptide fragments containing α-aminoisobutyric acid using Fmoc-amino acid chlorides/potassium salt of 1-hydroxybenzotriazole

The synthesis of peptides containing multiple Aib residues was accomplished using Fmoc-Aib-Cl in presence of KOBt. As no additional base was added, the duration of coupling reactions could be extended. Thus, the synthesis of the alamethicin 1-4 fragment, Aib-Pro-Aib-Ala, the emerimicin 2- 6 fragment, Aib-Aib-Aib-Val-Gly and the Aib tetramer, Fmoc-(Aib)4-OBzl were accomplished in good yield and purity.

Synthesis of Fmoc-amino acid chlorides assisted by ultrasonication, a rapid approach

The chloride derivatives of all common Fmoc-amino acids lacking polar side chains as well as a number of benzyl based side chain protection have been prepared using the corresponding amino acid and thionyl chloride assisted by ultrasound has been described. The protocol is simple, efficient and rapid. All the acid chlorides prepared have been obtained in good yield and purity.

Direct synthesis of Fmoc protected amino acid hydroxamates from acid chlorides mediated by magnesium oxide

The synthesis of Fmoc protected amino acid hydroxamates using Fmoc-amino acid chlorides and magnesium oxide is described. The method is simple and efficient, results in complete conversion, and gives good yields and satisfactory purity.

Practical and Efficient Synthesis of Orthogonally Protected α‐2,3‐Diaminopropionic Acid (2,3‐Dap), 2,4‐Diaminobutanoic Acid (2,4‐Dab), and their N‐Methylated Derivatives

Abstract The synthesis of orthogonally protected Fmoc‐Dap/Dab (Boc/Z/Alloc)‐OH starting from Fmoc‐Asp/Glu has been described. The salient features of our synthetic strategy involved formation of Fmoc‐Asp/Glu‐5‐oxazolidinone acids, conversion of acid function to acyl azides, Curtius rearrangement, and hydrolysis of the oxazolidinone group.

Microwave accelerated efficient synthesis of N-fluorenylmethoxycarbonyl/t-butoxycarbonyl/benzyloxycarbonyl-5-oxazolidinones

The synthesis of N-protected 5-oxazolidinones using amino acids, paraformaldehyde and p-toluene sulfonic acid in a minimum amount of toluene accelerated by microwave irradiation for 3 min in high yield is described.

Silicon tetrachloride and phenol as Nα-t-butoxycarbonyl group deprotecting agent in solid phase peptide synthesis

Abstract The combination of 1M silicon tetrachloride and 3M phenol serves as an efficient Nα-t-butoxycarbonyl deblocking agent in solid phase peptide synthesis, the duration of the cleavage being 10 min. This is demonstrated by the synthesis of the naturally occurring μ-receptor selective opioid heptapeptide, dermorphin.

Mw-enhanced high-speed deprotection of boc group using p-TsOH and concommitant formation of N-Me-amino acid benzyl ester p-TsOH salts

Abstract A high‐speed, complete deprotection of Boc group from Boc amino acids and protected peptide esters employing p‐TsOH in toluene under microwave irradiation is found to be complete in 30 s. The deprotection can be carried out in methanol and acetonitrile also. Under the present conditions, C‐peptide benzyl esters and O‐benzyl ethers have been found to be stable. This has permitted us to carry out the synthesis of [Leu]enkephalin employing the Boc/Bzl‐group strategy. Further more, it has been found that both N α‐Fmoc and N α‐Z groups are completely stable. The present conditions can be extended for the concomitant removal of the Boc group and the formation of C‐benzyl amino acid esters as well. This has been utilized for the synthesis of N‐Me amino acid benzyl esters starting from Boc‐N‐Me amino acids in a single step.