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The molecular and crystal structure of 2′(R)-mercapto-2′-deoxyneplanocin A, C11H13N5O2S M.W.=279.32, has been determined by X-ray analysis. The space group is P212121 with a=10.322(1), b=22.870(2), c=5.273(1)A and z=4. The structure was solved by direct method, and least-squares refinement using 1806 reflections with |Fo| > 30(F) led to the final R value of 0.045. The sugar C(2′) atom is displaced by 0.35A opposite to the base N(9), i.e., C(2′)-exo conformation and the torsion angle about the N(9)-C(1) bond is 26.3(4)° (anti conformation).

Neplanocin A (1) and N6-benzoylneplanocin A (2) were converted to the corresponding 3', 6'-O-(tetraisopropyldisiloxane-1, 3-diyl)-neplanocin A's (3, 4). The 2'-hydroxy group in 3 and 4 was triflated (5, 6). Nucleophilic displacement of 5 and 6 with a number of nucleophiles (I-, Br-, Cl-, N3-, AcO-, AcS-) in hexamethylphosphoric triamide afforded the corresponding 2' (R)-substituted derivatives in high yields. The 2' (S)-azido derivatives were obtained in a similar manner from arabinoneplanocin A prepared by this method. Adenosine was also converted to 2' (R)-substituted derivatives, including arabinofuranosyladenine, as well as 2' (S)-substituted adenosines. The physical properties of these 2'-substituted derivatives of neplanocin A and adenosine, including nuclear magnetic resonance and circular dichroism spectra, are presented.

Neplanocin A (I) was treated with 1, 3-dichloro-1, 1, 3, 3-tetraisopropyldisiloxane to give 3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) neplanocin A (II), which was converted to the 2'-O-trifluoromethanesulfonyl derivative (III). Nucleophilic substitution of III with a number of nucleophiles (AcO-, AcS-, N3-, Cl-, Br-, I-) in hexamethylphosphoric triamide afforded the respective 2' (R)-substituted derivatives in high yield. The halogenated derivatives were reduced with tri-n-butyltin hydride to the 2'-deoxy compound. 2'-O-Thiocarbonylimidazoyl-3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) neplanocin A was also reduced to the 2'-deoxy derivative. The deprotection of the bifunctional silyl group with tetra-n-butylammonium fluoride afforded 2' (R)-AcO, -AcS, -N3, -Cl, -Br, -I, and 2'-deoxy neplanocin A's, respectively. Physical data of these compounds including nuclear magnetic resonance, mass spectrum, and circular dichroism were given.

Phospholipase D from Streptomyces effectively catalyzed the transfer reaction of the phosphatidyl residue from phosphatidylcholines to the 5′-hydroxyl group of nucleosides in a two-phase system. A variety of 5′-phosphatidylnucleosides were easily prepared in high yields by this reaction.

Various carbocyclic nucleosides analogs of neplanocin A (such as 5-aminoimidazole-4-carboxamide riboside, uridine, 5-iodouridine, 4-thiouridine, cytidine, thymidine, 2′-deoxyguanosine, ribofuranosylthymine, a 2,2′-anhydroderivative, 2′-deoxycytidine, 2′-deoxythiouridine, and d -arabinofuranosylcytosine analogs) were synthesized from (1 R , 2 S , 3 R )-2,3-isopropylidenedioxy-4-methoxymethyloxymethyl-4-cyclopentenylamine. The cytidine analog was found the most active in inhibiting mouse lymphoma L5178Y cells in vitro at a concentration as low as 0.8 μg/mL.

Photolysis of 1-β-D-ribofuranosyl-5-aminoimidazole-4-carboxamide (AICA-riboside) gave 2-amino-N-(β-D-ribofuranosyl)malondiamide, which was cyclized by treatment with ethyl orthoformate to furnish 1-β-D-ribofuranosyl-5-hydroxyimidazole-4-carboxamide (bredinin), a potent immunosuppressive nucleoside antibiotic.

For deoxy analogues of N-acetyl-D-glucosamine and three deoxy-analogues of phenyl N-acetyl-β-D-glucosaminide were synthesized by means of chlorination with sulfuryl chloride and reduction of the chlorides with tri-n-butyltin hydride. The free sugars thus obtained failed to crystallize except for 6-deoxy and 4,6-dideoxy compounds. Phenyl glycosides were mostly crystalline. The yield of chlorination and reduction was generally high.

Benzyl 2-acetamido-6-O-acetyl-4-chloro-2,4-dideoxy-3-O-[D-1-(methyl carboxylate)ethyl]-α-D-galactopyrano-side and benzyl 2-acetamido-4,6-dichloro-2,4,6-trideoxy-3-O-[D-1-(methyl carboxylate) ethyl]-α-D-galactopyranoside were prepared by the reaction of sulfuryl chloride on N-acetyl-muramic acid derivatives. 2-Acetamido-2,4-dideoxy-3-O-(D-1-carboxyethyl)-D-xylohexo-pyranose (N-acetyl-4-deoxy-muramic acid) and 2-acetamido-2,4,6-trideoxy-3-O-(D-1-carboxyethyl)-D-xylohexo-pyranose (N-acetyl-4,6-dideoxy-muramic acid) were prepared by the reduction of these chlorodeoxy derivatives with tri-n-butyltin hydride.

A novel synthesis of bredinin by the conversion of AICA-riboside through a photo-degradation product is described.

Photolysis of 1-β-D-ribofuranosyl-5-aminoimidazole-4-carboxamide (AICA-riboside) gave 2-amino-N-(β-D-ribofuranosyl)malondiamide, which was cyclized by treatment with ethyl orthoformate to furnish 1-β-D-ribofuranosyl-5-hydroxyimidazole-4-carboxamide (bredinin), a potent immunosuppressive nucleoside antibiotic.

Bredinin 5'-oleyl and 5'-cetyl phosphates (2a and 2b), prepared from 1-β-D-ribofuranosyl-5-aminoimidazole-4-carboxamide via a photochemical ring-opening reaction of the imidazole moiety, showed remarkable antitumor effects against various transplantable mouse tumors, and were clearly superior to bredinin (1).

Phospholipase D from Streptomyces effectively catalyzed the transfer reaction of the phosphatidyl residue from 3-sn-phosphatidylcholine to the 5'-hydroxyl group of nuclesides in a two-phase system. Thus, a variety of 5'-(3-sn-phosphatidyl)nucleosides could be readily prepared in high yields by means of this reaction. Among them, phosphatidyl-FUR (3b), phosphatidyl-Ara FC (8b), and phoshatidyl-neplanocin A (12b) each produced a significant increase in the life span mice bearing i.p.-implanted P388 leukemia, being more effective than the parent nucleosides.

Phospholipase D from Streptomyces effectively catalyzed the transfer reaction of the phosphatidyl residue from phosphatidylcholines to the primary hydroxyl group of homoserine in a two-phase system. Various phosphatidylhomoserines were easily prepared in good yields by this reaction.

Phospholipase D from Streptomyces effectively catalyzed the transfer reaction of the phosphatidyl residue from phosphatidylcholines to the primary hydroxyl group of homoserine in a two-phase system. Various phosphatidylhomoserines were easily prepared in good yields by this reaction.

A novel synthesis of bredinin by the conversion of AICA-riboside through a photo-degradation product is described.

Neplanocin A (I) was treated with 1, 3-dichloro-1, 1, 3, 3-tetraisopropyldisiloxane to give 3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) neplanocin A (II), which was converted to the 2'-O-trifluoromethanesulfonyl derivative (III). Nucleophilic substitution of III with a number of nucleophiles (AcO-, AcS-, N3-, Cl-, Br-, I-) in hexamethylphosphoric triamide afforded the respective 2' (R)-substituted derivatives in high yield. The halogenated derivatives were reduced with tri-n-butyltin hydride to the 2'-deoxy compound. 2'-O-Thiocarbonylimidazoyl-3', 5'-O-(tetraisopropyldisiloxane-1, 3-diyl) neplanocin A was also reduced to the 2'-deoxy derivative. The deprotection of the bifunctional silyl group with tetra-n-butylammonium fluoride afforded 2' (R)-AcO, -AcS, -N3, -Cl, -Br, -I, and 2'-deoxy neplanocin A's, respectively. Physical data of these compounds including nuclear magnetic resonance, mass spectrum, and circular dichroism were given.