Biomedical subjects
Naoya Morohashi
Publications and source records attributed to Naoya Morohashi.
Interaction between quaternary ammonium ions and dipeptides: positive anion allosteric effect.
The binding properties of dipeptides possessing aromatic residues towards quaternary ammonium ions have been investigated by 1H-NMR spectroscopy. The intermolecular hydrogen bonding between exchangeable protons (OH and NH) of aromatic residues of dipeptides and the counter anion of ammonium ion is the primary force. After the formation of the intermolecular hydrogen bonding, two aromatic residues of dipeptides can provide pi-base cavity to interact with the quaternary ammonium moiety.
Stereoselective dialkylation of the proximal hydroxy groups of calix- and thiacalix[4]arenes.
Treatment of p-tert-butylcalix[4]arene (C1) and its sulfur-bridged analog T1 with 1,3-dichloro-1,1,3,3-tetraisopropyldisiloxane in the presence of imidazole gives proximally O,O'-disiloxane-1,3-diyl-bridged calixarenes C2 and T2 in excellent yields, respectively. Subsequent base-catalyzed etherification of the remaining hydroxy groups with alkyl halides gives syn- and anti-O'',O'''-dialkylated products, the stereoselectivity of which varies depending on the nature of the macrocycle, as well as the metal cation of the base employed. Thus, conventional calixarene C2 preferentially affords syn compounds of 1,2-alternate conformation (C3) with the aid of tert-BuOK and K(2)CO(3) and anti counterparts of partial-cone conformation (C4) with Cs(2)CO(3). On the other hand, thiacalixarene T2 affords syn compounds of 1,2-alternate conformation (T3) with any of the bases. The disiloxanediyl bridge of the resulting products can readily be removed by treatment with tetrabutylammonium fluoride. Thus, the net process provides an efficient method for the regio- and stereoselective synthesis of proximally dialkylated calix[4]arenes.
Synthesis, resolution, and absolute stereochemistry of (-)-blestriarene C.
A naturally occurring 1,1'-biphenanthrene, blestriarene C (1), was prepared in 13 steps and 30% overall yield. The key steps are the ester-mediated nucleophilic aromatic substitution on 2,6-di-tert-butyl-4-methoxyphenyl 5-isopropoxy-2-methoxybenzoate (4) by 2-methoxy-4-methoxymethoxy-6-methylphenylmagnesium bromide (5) and a novel intramolecular cyclization of the resulting 4-isopropoxy-2'-methoxy-4'-methoxymethoxy-6'-methylbiphenyl-2-carboxylic ester 14 to 7-isopropoxy-4-methoxy-2-(methoxymethoxy)phenanthren-9-ol (15). The racemic blestriarene C was optically resolved by chiral HPLC on a preparative scale to give several 10-mg yields of both the enantiomers in up to 95% ee. The absolute stereochemistry was determined to be S(a)-(-) by the axial chirality recognition method, which was based on the stereospecific formation of a 12-membered cyclic diester containing two biaryl-o,o'-diyl unites joined by ester -CO(2)- linkages. The validity of the method was confirmed by an X-ray crystallographic analysis and ab initio conformational analyses of such 12-membered cyclic diesters. It was found that blestriarene C and its 7,7'-diisopropyl ether 2 underwent rapid photoracemization even under ambient light exposure.
Synthesis of all stereoisomers of sulfinylcalix[4]arenes.
All four stereoisomers of p-tert-butylsulfinylcalix[4]arene [4(rccc), 4(rcct), 4(rctt), and 4(rtct)], arising from the disposition of the four sulfinyl groups with respect to the mean plane of the four bridging sulfur atoms, have been prepared via oxidation of p-tert-butylthiacalix[4]arene (2) or its tetra-O-benzyl ethers 5 of defined conformations. Thus, treatment of 2 with 4.4 molar equiv of NaBO(3).4H(2)O gave the rtct and rctt isomers in 27% and 17% yields, respectively, while oxidation of cone 5 (5(C)) and partial cone 5 (5(PC)) proceeded stereoselectively to give, after debenzylation of the resulting tetrasulfoxides 12 and 15, the rccc and rcct isomers in 56% and 28% yields, respectively, based on 5. The sulfinylcalix[4]arenes 4 were treated with iodomethane in the presence of a base to give the corresponding tetramethyl ethers 16, the structures of which in regard to the disposition of the sulfinyl groups and the conformation of the phenol units were determined by X-ray crystallography. Also reported is the synthesis of all four conformational isomers of tetra-O-benzyl ether of 2 (5(C), 5(PC), 5(1,2-A), and 5(1,3-A)).