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The unstable minor nucleosides, wyosine, wybutosine, and β-hydroxywybutosine, were isolated from tRNAs in sufficient amounts for determination of their structures.

The synthesis of the title compounds started with the Vilsmeier reaction of 3-[2,3,5- tris -O-(tert- butyldimethylsilyl)-β- d - ribofuranosyl]wye ( 5b ) and proceeded through the Wittig reaction with ( R )- N -(methoxycarbonyl)-3-(triphenylphosphonio)alaninate ( 4 ), methylation with trimethylsilyldiazomethane, OsO 4 oxidation, cyclocondensation with triphosgene, and catalytic hydrogenolysis. Chromatographic separation of the resulting diastereomeric mixture and subsequent deprotection afforded the two desired nucleoside [ [R-(R ∗ ,S ∗ )]- and [S-(R ∗ ,R ∗ )]- 2b ] for the first time.

Deoxygenation of the 1,2-glycol (±)-5 was achieved at the position adjacent to the heterocycle through the cyclic carbonate (±)-14, providing the monohydroxy compound 6. This new method of regioselective deoxygenation was employed for the first synthesis of β-hydroxywybutines [[R-(R ∗ ,S ∗ )]- and [S-(R ∗ ,R ∗ )]-2] : oxidation of the methyl butenoate 7 with osmium tetroxide, followed by deoxygenation through the cyclic carbonates (19 and 20), afforded the two diastereomers of 2.

Oxalyl chloride reacts with a wide range of acyclic 1,2-glycols 1 in the presence of triethylamine to produce 1,3-dioxolan-2-ones 3 together with 1,4-dioxane-2,3-diones 2. Ethylene glycol (1d), monosubstituted ethylene glycols 1e, j—l, and erythro-1,2-disubstituted ethylene glycols 1f, m, o provide the cyclic carbonates 3 as the minor products, while the threo-compounds 1g, i, n, p, q and pinacol (1h) afford 3 as the main products. The formation of 3 may be rationalized in terms of stereoelectronically controlled cleavage of the conjugate base 17− of the tetrahedral intermediates. The rate for the conformational change of 17− into 18− and the equilibrium constant between these conformers are proposed to be the major factors affecting the reaction pattern.

The title nucleoside 9 was synthesized by alkylation of 8-oxoadenosine ( 7 ) with 4-benzyloxy-3,5-dibromobenzyl bromide, followed by Dimroth rearrangement and acid hydrolysis. 2′-Deoxy version of this reaction sequence accomplished the first synthesis of aplidiamine ( 6 ).

The Wittig reaction of 1-benzyl-7-formylwye (12) with (R)-[2-carboxy-2-[(methoxycarbonyl)amino]ethyl]triphenylphosphonium chloride (8) followed by successive methylation and reduction gave (-)-wybutine [(S)-1a].

[ R -( R *, S *)]-e-Hydroxywybutine ( 6 ) and its [ S -( R *, S *)]-isomer ( 9 ) have been synthesized as the most probable alternatives for hydroxy-Y base isolated from rat liver phenylalanine tRNA.

On the basis of the chiral syntheses of (1′R)-I and (1′S)-I and of their 9-ribosides (1″R)-III and (1″S)-III from D- and L-alanines, the structures of the cytokinins 1′-methylzeatin and its 9-riboside have been established to be (1′R)-I and (1″R)-III.

The first synthesis of the antitumor antibiotic guanine 7-oxide (VI) has been achieved via a 4-step route starting from phenacyl bromide (I) and the nitropyrimidone III and proceeding through the intermediates IVe and Ve.

Synthesis of 3,9-dialkylguanines 5 has been accomplished by N-cyanation of 1-alkyl-5-(alkylamino)imidazole-4- carboxamides 3 followed by base-catalysed cyclisation. Cyclocondensation of 9-alkyl-3-methylguanines 5a, d, f with MeCOCH2Br gave 3-alkylwyes 6, model compounds of the most probable structure for wyosine from Torulopsis utilis tRNAPhe.

An improved synthesis of the key intermediate 5 for the chiral syntheses of wybutine (1c) and hydroxywybutine (1d) has been achieved by palladium-catalyzed vinylation, which has been utilized for the first synthesis of 3-β-D-ribofuranosylwybutine (2c).

The reaction of adenine 1-oxide (II) with alkyl halides in N,N-dimethylacetamide resulted in O-alkylation. These 1-alkoxyadenine salts (III) were readily converted into the corresponding free bases (IV). The alkylation of IV m a similar manner gave 1-alkoxy-9-alkyladenine salts (V) in 52–71 % yield. This method was applied to the synthesis of 9-alkyladenines (VII), by transformation of the free bases (VI) of 1-alkoxy-9-alkyladenines into VII by catalytic hydrogenolysis over Raney nickel.

The rates of the Dimroth rearrangements of l-alkoxy-9-alkyladenines (I) and 1-alkyl-9-methyladenines (V) have been measured. It is shown that 1-alkoxy derivatives (I) undergo rearrangement to give isomeric 6-alkoxyamino derivatives (III) through isolable monocyclic intermediates (II) and that these intermediates also suffer hydrolysis leading to deformylated derivatives (IV) in competition with their reclosure to III. In the I-alkyl series, no intermediates have been detected and thus the observed first-order rate constants for the rearrangements may be regarded as those for the ring-opening of V. Comparison of the rate constants for 1-methoxy-9-methyladenine (Ia) and 1,9-dimethyladenine (Va) reveals that at pH 7·60 and above Va rearranges more rapidly than Ia, although the latter undergoes ring- opening ca. 30 times as fast as the former. In each of both compounds ring-opening proceeds at a rate proportional to hydroxide ion concentration below pH 8·5 and above pH 11, with a plateau between the two values. These results are consistent with attack by the hydroxide ion on both the protonated and neutral species of the adenine derivatives.

The Dimroth rearrangement of 1-alkoxy-9-alkyladenines (Ia,b,c,d) to 6-alkoxyamino-9-alkylpurines (IIa, b, c, d) was readily effected by treating the free bases (I) with boiling water. On the other hand, treatment of the 1-alkoxy derivatives (Ia, b, c) with water at a lower temperature produced N′-alkoxy-1-alkyl-5-formamidoimidazole-4-carboxamidines (IVa, b, c), the intermediates in the Dimroth rearrangements, in good yields. When heated in water, IVa, b,c were recyclized to the rearranged products (IIa, b, c) with formation of a trace of the reversion products (Ia, b,c). The reaction of I with hot aqueous alkali afforded N′-alkoxy-1-alkyl-5-aminoimidazole-4-carboxamidine (III), the deformylated product of IV, and a small amount of the rearranged product (II). Treatment of IVc with alkali also gave IIIc and a small amount of IIc, whereas the reaction with acid resulted in the rapid reversion to Ic.

3-Methylisoguanosine (4c) has been synthesized from 5-(cyanomethylamino)-1(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)imidazole-4-carboxamide (1b) through the carbonitrile (2b).