Oligodeoxyribonucleotides were synthesized using H-phosphonate monomers without amino protection. The H-phosphonate monomers of deoxyadenosine, deoxycytidine, and deoxyguanosine bearing the free amino groups were synthesized in good yields by O-selective phosphonylation of the parent 5‘-O-(dimethoxytrityl)deoxyribonucleosides. It was found that the amino groups of the nucleosides were not modified during internucleotidic bond formation where (benzotriazol-1-yloxy)carbonium and -phosphonium compounds were employed as condensing reagents. The most effective condensing reagent for rapid internucleotidic bond formation was found to be 2-(benzotriazol-1-yloxy)-1,1-dimethyl-2-pyrrolidin-1-yl-1,3,2-diazaphospholidinium hexafluorophosphate (BOMP). In the present H-phosphonate method, 2-(phenylsulfonyl)-3-(3-nitrophenyl)oxaziridine (PNO) was employed as a new oxidizing reagent for the oxidation of internucleotidic H-phosphonate linkages under anhydrous conditions in the presence of N,O-bis(trimethylsilyl)acetamide. The reaction mechanism for the O-selective condensation was investigated in detail by means of 31P NMR spectroscopy. Unprecedented oxidation of the H-phosphonate monomers was observed during activation of the monomers with (benzotriazol-1-yloxy)phosphonium and -carbonium condensing reagents in the absence of the 5‘-hydroxyl components. A mechanism for the O-selective condensation was proposed on the basis of ab initio molecular orbital calculations for the model compounds at the HF/6-31G* level.

Abstract-Effects of sulpiride on the central nervous system were studied in catalepsy induction (I) and antagonism to gnawing behaviour (I1) induced by apomorphine and methamphetamine in normal rats, and in antagonism to rotational behaviour (II1) induced by apomorphine and methamphetamine in rats with substantia nigra uni laterally lesioned chronically by microinjection of 6-hydroxydopamine. Sulpiride was administered orally and intraventricularly, and the effects of sulpiride were com pared to those of haloperidol and chlorpromazine administered through the same routes. In oral administration, sulpiride was almost inactive in (1), and was several hundreds to a thousand times less potent than haloperidol in (II) and (III), while chlor promazine was 20 to 150 times stronger than sulpiride. In intraventricular admin istration, sulpiride was almost equipotent to haloperidol in (I), and was equally effective to or 2 to 3 times more effective than halopridol in (III), although several times less potent than haloperidol in (I1), and chlorpromazine was least potent among the drugs in all respects. These findings suggest that sulpiride is essentially a potent inhibitory substance on dopamine receptors in the central nervous system and the rather weak central effects of peripherally given sulpiride are due to poor penetration through the blood brain barrier.

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