Synthesis and biological activity of hydroxylated analogs of RCAI-80

RCAI-80 is one of the ester analogs of KRN7000 (α-galactosylceramide). This compound released mainly T helper 2 (Th2) cytokines, such as IL-4 rather than T helper 1 (Th1) cytokines, such as IFNγ from the invariant natural killer T (iNKT) cells. In addition, it has been known that some of the hydroxylated derivatives of KRN7000 make the cytokine secretion bias to Th2 by decreasing the IFNγ production to almost zero. This time, the three compounds having these two characteristic properties, namely an ester group and also some extra hydroxy groups existing on the ester side chain and/or on the 2-acyloxy-3,4-dihydroxyoctadecyl main chain of RCAI-80, were synthesized to examine the biological activities. As a result, it was found that these compounds made the cytokine secretion skew to Th2. Therefore, their effectiveness for experimental autoimmune encephalomyelitis (EAE) was examined. It was recognized that one of them showed moderate suppression of EAE symptom.     

Studies directed toward synthesis of guanosine 8,5''-imino cyclonucleosides and derivatives—I

8,5'-Aminimino bridging in the guanosine series using 5'-O-tosyl (1) and 5'-O-mesyl derivatives (2) of 2',3'-O-isopropylidene-8-bromoguanosine (5) and hydrazine gave N³,5'-cyclized product 3 and the N⁵,5'-cyclonucleoside of 4-carboxyhydrazido-5-amino-2-bromoimidazole 4. To exclude the N³,5'-cyclization through ionization in the base moiety, a N²-dimethylaminomethylidene-N¹-methoxymethylene derivative 7 was synthesized from 5 through the N²-protected compound 6. 7 was converted into the N²-dimethylaminomethy analogue 8, which with hydrazine yielded first the N²-deprotected form of 8 (9). 8 or 9 with hydrazine under forcing conditions gave an 8,5'-aminimino-N¹-methox derivative 10. Oxidation of 10 with sodium metaperiodate or sodium nitrite yielded 8,5'-imino-N¹-methoxymethyleneguanosine (11a) and 8,5'-imino-N¹-methoxymethylenexanthosine derivative 11b, respectively. 11a was deprotected to 8,5'-imino-N¹-methoxymethyleneguanosine 12.     

Reactions of the derivatives of 5,6-diaryl-2,5-dihydro-1,2,4-triazines with dimethyl acetylenedicarboxylate—structural reassignments of the products and further observations

The structures of the dihydro derivatives of 5,6-diaryl-1,2,4-triazines and of the products from the title reactions have been reassigned as 5,6-diaryl-2,5-dihydro-1,2,4-triazines ($\text{5}$a-g) and 2,6-diaryl-4-methyl-5-substituted-1,8-bis-methoxycarbonyl-3,4,7-triaza-bicyclo[3.3.0]octa-2,7-dienes ($\text{7}$a-g), respectively.     

Certain relative quadric hypersurfaces in 3-dimensional projective space bundles over a projective curve

We classify the certain type of relative quadric hypersurfaces of 3-dimensional projective space bundles over a projective line or an elliptic curve whose fiber is the direct product of 2 projective lines.