Of P-lapachone

Prof. Burton has recently prepared and characterized (by NMR) benzo[a] phenazines obtained by condensation of P-lapachone with 1,2-phenylenediamines [128]. 

A new photochemical conditions with catalytic quantities of P-lapachone have been recently reported [140]. The P-lapachone acts as photosensitizer to promote selective C16-C21 bond cleavage of catharanthine (65) yielding 21a-cyano-16a-(methoxycarbonyl) cleavamine (66) quantitatively, Fig. (13). 

Two short syntheses of P-lapachone from readily available naphthols and 3-methylbut-2-enal via a mild phenyl-boronic acid mediated cyclization to 2//-chromenes have been reported. Catalytic hydrogenation of 2H-chromenes with H /Pd-C in ethyl acetate afforded the corresponding naturally occurring chromanes (72) and (73). Oxidation of the adequate chromane with an excess of cerium ammonium nitrate (CAN) furnished P-lapachone in 62% yield [153]. 

Barnes et al have carried out the synthesis of P-lapachone in eight steps with an overall yield of 23% starting from a-naphthol. The yields from... 

Some synthetic lapachol derivatives have also showed cytotoxic activity. Burton et al have prepared mono(arylimino) derivatives of P-lapachone. Some of these derivatives had good scores with net cell kills in preliminary in vivo testing hollow fiber assays against a standard panel of 12 human tumor cell lines [160].Twelve substituted 1,4-naphthoquinones were tested against the ascitic form of sarcoma 180 in Swiss mice. Statistical analysis showed that the most important molecular parameter determining their effectiveness in prolonging the life of mice bearing this tumor is their redox potentials [161]. Zalkow et al have synthesized a monoimine quinone, namely 2-methyl-(Z)-4-phenylimino)naphth[2,3-d]oxazol-9-one, which in in vitro tests showed a selective activity for some solid cancer tumors [162]. Enamine derivatives of lapachol were... 

Snieckus et al have developed a general combined metalation-cross coupling methodology, and its application to a short synthesis of P-lapachone, Fig. (19) [155]. 

Irradiation of the herbicide metamifop (50) leads to A-(2-fluorophenyl)-A-methyl-2-hydroxypropionamide as major product. Minor amounts of A-methyl-2-fluoroaniline and A-methyl-A-phenyl-2-oxopropionamide are also obtained." Laser flash photolysis of p-lapachone-3-sulfonic acid (51) gives the triplet excited state, which is efficiently quenched by electron rich amino acids via electron transfer followed by proton transfer. No measurable quenching is observed in the presence of thymine or thymidine by contrast, the reaction with 2 -deoxyguanosine is fast, although not diffusion-controlled. The singlet oxygen quantum yield, determined by time-resolved near-IR emission, is ca. 0.7. "... 

Silva RSF, Guimaraes TT, Teixeira DV, Lobato APG, Pinta MCFR, de Simone CA, Soares JG, Cioletti AG, Goulart MOF, Pinto AV (2005) The preparation of a 10-membeied ring macrolactone by selective ozonolysis and the role of the dihydropyran-substituent on the MCPBA-oxidation reaction profile of p-lapachone phenazines. J Braz Chem Soc 16(5) 1074-1077. doi 10.1590/S0103-50532005000600027... 

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