Facile access to 2'-O-acyl prodrugs of 1-(β-D-arabinofuranosyl)-5(E)-(2-bromovinyl)uracil (BVAraU) via regioselective esterase-catalyzed hydrolysis of 2',3',5'-triesters.

Treatment of 1-​(2,​3,​5-​tri-​O-​acetyl-​β-​D-​arabinofuranosyl)​-​5-​[2-​(trimethylsilyl)​-​vinyl]​uracil with pyridinium bromide perbromide and deacetylation gave BVAraU I (R = H)​. Pig liver esterase (EC 3.1.1.1) catalyzed the regioselective hydrolysis of 1-​(2,​3,​5-​tri-​O-​acyl-​β-​D-​arabinofuranosyl)​uracil derivs. to their 2'-​O-​acyl monoesters, e.g. I [R = Ac, Bz, Me(CH2)​3CO]​

A new direct glycosylation of pyrimidine, pyrazole, imidazole and purine heterocycles via their N-tetrahydropyranyl (THP) derivatives

Pyrimidine, pyrazole, imidazole and purine N-tetrahydropyranyl (THP) derivatives have been converted in one-pot and in a regio- and stereo-selective manner into the corresponding β-D-2′,3′,5′-tri-O-benzoyl ribofuranosyl nucleoside derivatives on treatment with 1-β-acetyl-2′,3′,5′-tri-O-benzoyl-ribofuranose, hexamethyldisilazane (HMDS), trimethylsilyl chloride (TMSCI), and trimethylsilyl triflate (TMST)

An effect synthesis of 4-oxo-2,5-hexadienoates via D2-isoxazoline intermediates

An efficient method for the prepn. of 4-​oxo-​2,​5-​hexadienoates starting from 3,​5-​disubstituted Δ2-​isoxazolines is described. The N-​O bond cleavage of the isoxazoline ring, promoted by molybdenum hexacarbonyl, afforded the β-​hydroxy ketone intermediates (E)​-​4-​R1C6H4CH:CHCOCH2CH(OH)​CO2R (R = Me, Et; R1 = H, NO2, Me, OMe) which were smoothly dehydrated to the expected 4-​oxo-​2,​5-​hexadienoates (E,​E)​-​4-​R1C6H4CH:CHCOCH:CHCO2R in about 40​% yields

Geiparvarin analogs. 2. Synthesis and cytostatic activity of 5-(4-arylbutadienyl)-3(2H)-furanones and of N-substituted 3-(4-oxo-2-furanyl)-2-buten-2-yl carbamates.

In an attempt to determine some of the structural features of geiparvarin (1) that account for ita cytostatic activity in vitro, a series of geiparvarin analogues (loa-i, 1, 12, and 14-16) which contain novel modifications in the region of the olefinic double bond and of the coumarin moiety have been designed and synthesized.' Among the derivatives containing a carbamate moiety, only the analogues containing a carbamate group linked to an alkyl moiety lob-i were endowed with potent cytostatic activity, whereas the corresponding benzene derivative 10a was devoid of any antiproliferative activity. 6-Methoxygeiparvarin 101 proved equally effective as geiparvin (l), while compounds containing an additional double bond at the side chain (12 and 14-16) were invariably 5-1Wfold less effective than geiparvarin. Diene derivative 15, bearing a coumarin moiety, was essentially inactive against murine (L1210, FM3A) tumor cells but exhibited good activity against human (Molt/4F, MT-4) tumor cell

Retinoic acid conjugates as potential antitumor agents: Synthesis and biological activity of conjugates with Ara-A, Ara-C, 3(2H)-furanone, and aniline mustard moieties

In a dual targeting approach, to explore the ability of tretinoin (all- trans-retinoic acid) to behave as a covalent carrier for cytotoxic entities, conjugates of retinoic acid with a few representative molecules, being important examples of antitumor pharmacophores (i.e., nucleoside analogues and alkylating agents), have been synthesized and tested for their cytostatic and differentiating activity. All compounds were stable to in vitro hydrolysis in human plasma and more lipophilic than the parent compounds, thus consenting enhanced uptake into the cells. Among the nucleoside analogues the Ara-C derivatives 3 and 6 and the Ara-A derivative 7 proved the most cytostatic (IC50 144-fold more active (Ara-A derivatives) or at least as equally active (Ara-C derivatives) as compared to the parent nucleosides. Compound 3, endowed with a highly lipophilic silyl moiety at the 3' and 5' positions, showed the highest differentiating activity (54% and 44% differentiated HL-60 cells at 0.2 and 0.05 μg/mL respectively). With regard to the retinoic acid conjugates of alkylating agents, compound 10 was the most cytostatic agent (IC50 < 0.32 μg/mL) and the most potent differentiating agent (33-34% at 0.32 and 0.08 μg/mL). These structures may also be regarded as analogs of either retinoic acid or the cytotoxic compound