Oxazine moiety

Opening of the six-membered oxazine moiety of some [l,2,3]triazolo[5,l-c][l,4]oxazines was studied by Hoornaert et al. < 1994TL9767, 1996T8813>, and the result is shown in Scheme 9. Ring opening of 75 took place in alcohol or refluxing aqueous acetonitrile for 15 min to yield the [l,2,3]triazole derivative 76 in most cases in high yield. As nucleophiles, aliphatic alcohols, ammonia, or water were used. 

The triazoloxazine 294 containing the saturated oxazine moiety was synthesized by Knight and Leeper <1998J(P1)1891> treatment of the hydrazinium salt 293 with trimethyl orthoformate yielded the product 294 in quantitative yield. 

The acetic anhydride-induced cyclodehydration of the symmetrical diamide 411, derived from the tetrahydro-benzothiophene / -amino ester 410 and diethyl malonate, afforded the thieno[2,3-r7 [h3]oxazine derivative 413 rather than the expected bis-oxazine 412 (Scheme 78). The reaction probably takes place through sequential cyclizations, in which the pyridine ring of 413 is produced by condensation of the exocyclic double bond of the enamine tautomeric form of the 1,3-oxazine moiety and the mixed anhydride formed by the carboxylic group and acetic anhydride <2003PS245>. 

Guglielmetti et al. 10 reported compounds 13 and 14 having the heteroatoms in the oxazine moiety. These series of the spiropyrimidobenzoxazines and spirothia-zolobenzoxazines extended the available range of photochromic properties. 

Conformation analysis of isomeric perhydropyrido[l,2-c][l,3]benzoxa-zines (21-24) by means of NMR studies demonstrates that the predominant conformers of the isomers 21, 22, and 23 contain a frans-fused pyrido[l,2-c][l,3]oxazine moiety, whereas that of 24 has an O-outside cw-fused pyrido[l,2-c][l,3]oxazine moiety (see Scheme 6) (70T1217 71TL3361). 

The biosynthesis of minimycin was studied in Streptomyces hygroscopicus by Isono et al. using a variety of radio-labeled precursors. They proposed a C-7 sugar or a C-8 branched sugar as a possible biosynthetic intermediate for both the ribose and oxazine moieties of minimycin [371]. Two years later, the same authors reinvestigated the biosynthesis of this nucleoside and reached the conclusion that the glutamate is a biosynthetic precursor for the biosynthesis of minimycin [372]. 

The presence of the tetrahydro-l,2-oxazine moiety was also proven by means of chemical degradation (Scheme 7). The reduction of 6 over 10% palladium on charcoal furnished dihydrophyUanthidine (73). Further hydrogenolysis of 73 followed by acetylation yielded the N,0-diacetyl derivative 74. 

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