Chiral alpha-aminoxy acid/achiral cyclopropane alpha-aminoxy acid unit as a building block for constructing the alpha N-O helix.

The monomer 1 derived from achiral 1-(aminoxy)cyclopropanecarboxylic acid (OAcc) and oligopeptides 2-9 consisting of a chiral alpha-aminoxy acid and an achiral alpha-aminoxy acid such as OAcc were synthesized and their structures characterized. The eight-membered-ring intramolecular hydrogen bond, namely the alpha N-O turn, was formed between adjacent residues independent of their chirality. However, the helix formation was sequence-dependent. Dipeptide 2 bearing chiral alpha-aminoxy acid (d-OAA) at the N-terminus and achiral OAcc at the C-terminus preferentially adopted a right-handed 1.8(8) helical structure, but dipeptide 3 (OAcc-d-OAA) did not. Theoretical calculation results, in good agreement with experimental ones, revealed that the biased handedness of alpha N-O turn found in OAcc residue depends on its preceding chiral residue. It was then found that the helical conformation was destroyed in the case of oligopeptides 6 and 7 [OAA-(OAcc)(n), n = 2, 3]. The crystal structure of tripeptide 8 ((i)PrCO-d-OVal-OAcc-d-OVal-NH(i)Bu) further disclosed the helical structure formed by three consecutive homochiral alpha N-O turns. This study has uncovered achiral aminoxy acid residues such as the OAcc unit as a useful building block to be incorporated into chiral aminoxy peptides to mimic chiral helix structure.

Disulfide bond creates a small connecting loop in aminoxy peptide backbone.

Disulfide-bond formation between the side chains of cysteine-cysteine pairs is often critical to the folding behavior, stability, and functionality of proteins. In this paper, we report that sulfur atoms can be introduced into the amide groups of aminoxy peptides to form a novel type of disulfide bridge, which creates a connecting loop in the peptide backbone.

A regioselective cyanohydration of steroidal 17-ketones and the configuration of the resulted cyanohydrins.

Cyanohydration of some 17-keto steroids with 4-en-3-one or 1,4-dien-3-one unit showed high regioselectivity to give 17-cyanohydrins with high yields when the reaction was carried out under acetone cyanohydrin/K2CO3 in aq. MeOH. The crystal X-ray exhibited the configuration of resulted cyanohydrins were depended on the structure of substrates.

Crystallographic determination of stereochemistry of biologically active 2'',3''-dibromo-7-epi-10-deacetylcephalomannine.

The stereochemistry at C2'' and C3'' of two diastereomers of 2'',3''-dibromo-7-epi-10-deacetylcephalomannine (6 and 7), which were synthesized by reacting 7-epi-10-deacetylcephalomannine (5) with bromine, were assigned unambiguously based on crystallographic studies of 6. The X-ray crystallographic analysis shows that 6 adopts an absolute configuration of (2''S,3''R), and 7 can be assigned as (2''R,3''S) configuration. The side-chain conformation of 6 was revealed to be different with the known hydrophobic collapse and the apolar conformations, as found in solid state and in solution. However, most side-chain torsion angles of 6 were found to be very similar to those of tubulin-bound T-shaped conformation (T-Taxol). Both 6 and 7 showed strong in vitro paclitaxel-like activity.

A new photochromic tetrahydroindolizine.

The title compound, dimethyl 10b'-(4-fluorostyryl)-8',9'-dimethoxy-4-nitro-5',6'-dihydrospiro[9H-fluorene-9,1'(10b'H)-pyrrolo[2,1-a]isoquinoline]-2',3'-dicarboxylate, C38H31FN2O8, is a new photochromic tetrahydroindolizine. One of the C-C bonds at the spiro C atom is very long [1.630 (2) A], thus explaining the photochromic behaviour.