D-4-Oxo

ANTIBIOTICS - NUCLEOSIDES AND NUCLEOTIDES] (Vol 3) 7-(b-D-Ribofuranosyl)-4-oxo-3H,5H-pyrrolo[3,2-d]pyrinndine... 

Most recendy the stmcture of pyrrolosine has been shown to be an isomeric C-nucleoside analogue of 9-dea2ainosine, which is 7-(P-D-ribofuranosyl)-4-oxo-3Ff,5E -pyrrolo[3-2-i/ pyrimidine (29). Pyrrolosine inhibits development of starfish embryos. 

H-Furo[3,4-e]pyrazole, 1,4-dihydro-4-oxo-l-substituted synthesis, 6, 989 Furo[2,3-d]pyrazoles synthesis, 6, 998 Furo[3,4-d]pyrazoles synthesis, 6, 998 Furo[2,3-d]pyridazine H NMR, 4, 984 synthesis, 4, 984... 

The irradiation of 2-methoxytropone (A) leads to methyl 4-oxo-2-cyclopentenyl-acetate (D). The reaction can be followed by analytical gas chromatography and two intermediates are observed. These have the structures B and C. Indicate a mechanism by which each of the three successive reactions might occur. The first two steps are photochemical, while the third is probably an acid-catalyzed reaction which occurs under the photolysis conditions. 

The same amino compounds also underwent reactions with a series of 3-cyano-4-imino- and 3-cyano-4-oxo-piperidines to yield 4-amino-5,0,7,8-tetrahydropyrido[4,3-d]pyrimidines. . A tetra-hydropyTido[4,3-prepared from 4-amino-l-henzyl-3-cyano-d -piperidine (134) hy a simple one-step preparation. This method is of general application for the preparation of fused pyrimidines and previous papers in this field are listed by Taylor. ... 

The catalytic effect of protons has been noted on many occasions (cf. Section II,D,2,c) and autocatalysis frequently occurs when the nucleophile is not a strong base. Acid catalysis of reactions with water, alcohols, mercaptans, amines, or halide ions has been observed for halogeno derivatives of pyridine, pyrimidine (92), s-triazine (93), quinoline, and phthalazine as well as for many other ring systems and leaving groups. An interesting displacement is that of a 4-oxo group in the reaction of quinolines with thiophenols, which is made possible by the acid catalysis. 

Triazanaphthalenes (446) substituted with a single leaving group have been little studied. 4-Aminopyrido[3,2-d]pyrimidine and its 6-methyl derivative have been hydrolyzed with 5N acid (100°, 30 min) and lOA alkali (95°, 3 hr, 10% yield).Attempted replacement of the 4-oxo group (via acyloxy intermediates) with phosphorus oxychloride or pentasulfide failed,in contrast to the successful replacement in the more activated 4-oxo-l,3,8-triaza analog discussed below. Similarly, the 2,4-dioxo derivative could not be thionated with the pentasulfide, and its reaction with the oxychloride was less facile than that of the 2,4-dioxo-l,3,8-triaza compound. 

Only a few displacements involving mono-substituted compounds are known. 4-Chloropyrido[2,3-d]pyrimidine reacts readily (96°, 30 min) with aqueous aniline, hydrazine, or ammonia and with diethylamine (0°, 16 hr). In contrast to the 1,3,6-isomers, the 4-oxo and 2,4-dioxo derivatives are readily converted into chloro and thioxo derivatives by phosphorus oxychloride and pentasul-... 

Oxidation reactions were used in the synthesis of porphyrin d, the metal-free ligand system of naturally occurring heme d,. In a total synthesis of porphyrin d,12d oxo functions were introduced into isobacteriochlorin 3 by selenium dioxide oxidation to yield 4. The selenium dioxide selectively attacks the 3- and 8-positions of the partially reduced pyrrole rings of the chromophore. In another synthesis23a c of porphyrin d, an isobacteriochlorin 5, derived by... 

Methylmagnesium chloride has been added to various d-(4-substituted-phenyl) <5-oxo esters 15 (X = H, Cl 13, F, Cl, Br, OC11,) which provides the diastereomeric -lactones 1642. The electronic properties of the phenyl 4-substituent have no significant influence on the diastereoselectivity. Except for the 4-methoxyphenyl compound, which is unreactive even at 60 °C, a ratio of ca. 40 60 in favor of the anti-Cram product is observed at 60 "C in tetrahydrofuran as reaction solvent. Lowering the reaction temperature to 0 °C slightly increases the anti-Cram selectivity in the case of the 4-fluoro-, 4-chloro-, and 4-bromo-substituted compounds. On the other hand, a complete loss of reactivity is observed with the <5-phenyl- and <5-(4-methylphenyl)-substituted h-oxo esters. 

Losung der 4-Oxo-pentansaure in Diglyme soil 4-Pentanolid (44% d. Th.) entstehen. 

Wahrend iiberschiissiges Natrium-bis-[2-methoxy-athoxy]-dihydrido-aluminat 4-Oxo-pentansaure zu Pentandiol-( 1,4) (67% d.Th. 80°, Toluol) reduziert, erhalt man mit 1,1-Molaquivalenten Reduktionsmittel 4-Pentanolid (57% d.Th. bei —20°, inverse Zu-gabe)1. 

Analog erhalt man aus 4-Oxo-l-benzyl-3-athoxycarbonyl-piperidin 4-Hydroxy-3-hydroxymethyl-1 -benzyl-piperidin (41,7% d.Th. Kp0.03 142-146°). 

Oxo-4H- (benzo-[d]-1,3-oxazine) werden durch Lithiumalanat unter Bildung der 2-Acylaraino-benzylalkohole aufgespalten1. Mit Natriumboranat bilden sich da-gegen ahnlich wie bei den 2H-Pyronen (s. S. 445) auch die entsprechenden 2-Alkylami-no-benzoesauren z. B.2 ... 

Wahrend 4-Oxo-l,4-dihydro-chinazoline mit Natriumboranat entweder unter Erhalt der Lactam-Struktur reduziert oder reduktiv gespalten werden (s. S. 352f.), erhalt man aus 4-Oxo-l-phenyl-l,2,3,4-tetrahydro-chinazolin mit Lithiumalanat 2-(Methylamino-me-thyl)-N-phenyl-anilin (84% d.Th.). 

Methylaminomcthyl-N-phenyl-anilin 1.5 g (6,7 mMol) 4-Oxo-1-phenyl-1,2,3,4-tetrahydro-chinazolin werden unter Stickstoff mit 0,75 g (20 mMol) Lithiumalanat in 15 ml abs. Diathylather 4 Stdn. unter RuckfluB er-hitzt. Man kiihlt ab, vcrsetzt mit 0,8 ml Wasser, 0,8 ml 15%iger Natriumhydroxid-Losung und 2,5 ml Wasser, fil-triert und wascht mit Diathylather, trocknet das Filtrat mit Magnesiumsulfat, engt ein und destilliert Ausbeute 1,2 g (84°/, d.Th.) F 96-97° (Acetyl-Derivat). 

Aus 2-Methoxy-4-oxo-4-phenyl-buten-(2) erhalt man auf analoge Weise 92% d.Th. 3-Oxo-l-phenyl-buten3. Sind weitere mit Lithiumalanat reduzierbare Gruppen vorhan-den, so wird vor allem Natriumboranat eingesetzt z.B.4 ... 

Gelegentlich wird auch Lithiumboranat als Reduktionsmittel eingesetzt. 4-Oxo-4-phe-nyl-butansaure liefert z.B. in Tetrahydrofuran 4-Phenyl-butan-4-olid (78% d.Th.)9. 

Athvlaniin<>-pyridin-2-carbonsaure-anilid5 1 g (3,6 mMol) 4-Oxo-2-methyl-3-phenyl-3,4-dihydro-(pyri-do-[3,2-d]-pyrimidin) und 0,65 g (17 mMol) Natriumboranat werden in 20ml Isopropanol bei 20° 20 Stdn. ge-riihrt. Man verdiinnt mit Wasser, schiittelt mit Chloroform aus und kristallisiert den Riickstand aus Petrolather Ausbeute 0,71 g (72"/ d.Th.) F 65-66°. 

Oxo-l-tert.-butyl-cyclohexan tert.-Butyl-cyclohexan 77% d.Th. 

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