Of a-lapachone

Because of such extensive application in folk medicine, it is easy to understand the interest that the lapachol, the related naphthoquinones a-lapachone, P-lapachone and other naphthoquinones derivatives, have aroused as potential drugs. In fact, a broad variety of biological activities have been described for this kind of compounds. Some examples are antitumor promoting activities [11-12], inactivators of human cytomegalovirus protease [13], antiprotozoal activity [14], trypanocidal activity [15], anticancer activity [16], and antibacterial and antifungal activities [17]. 

The work realized by Dauson et al [127] is of particular interest for the H NMR and 13C NMR assignments of these type of molecules. The isomers a-lapachone and P-lapachone can be easily distinguished, attending to the pattern that present the linear and angular pyranonaphthoquinones in their NMR spectra. In the H NMR spectra, the signals corresponding to the aromatic protons appear in two different forms. In the case of a-cycled compounds, the aromatic protons have a symmetric environment and the hydrogens H5 and Hg are equivalent as... 

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

Although it presents diverse stereogenic centers, the authors do not indicate if this compound was found as a racemic mixture. Dehydro-a-lapachone (58) and dehydro-p-lapachone (59) are formed by oxidative cyclisation of lapachol with DDQ [134-135]. The reduction of quinones to hydroquinones is a quick, quantitative, and reversible process, which is common both to ortho and para quinones [136]. The transformation of lapachol to p-lapachone in acid media was treated previously in section-2. 

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). 

Syntheses of a- and p- lapachones and their homologues were carried out by photochemical side chain introduction to quinone. Thus, 1,4-naphthoquinone photochemically reacted with 3-methyl-2-butenal to give 2-(3-methyl-2-butenoyl)-l,4-naphthalenediol (69), regiospecifically. The product (69) was successively treated with acid, with dichloroaluminiun hydride, and finally with iron (III) chloride to derive in turn to cromanon (70), dihydropyran (71), and P-lapachone (35). P-lapachone was easily transformed to a-lapachone (38) by treating with acid. Likewise, from... 

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]. 

Snieckus et al have developed a general combined metalation-cross coupling methodology, and its application to a short synthesis of 0-lapachone, Fig. (19) [155]. 

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... 

It has been recently reported by Nair et al an efficient protocol for the synthesis of a, P-lapachones derivatives based on hetero Diels-Alder trapping of 3-methylene-1,2,4-[3//] naphthalenetrione [158]. 

BIOLOGICAL ACTIVITY OF LAPACHOL, a-LAPACHONE, 0-LAPACHONE AND THEIR DERIVATIVES... 

Biological investigations over the last years have shown that many of the medicinal properties claimed for Lapacho, Taheebo, Pau D Arco or Ipe Roxo are attibuted to the active components lapachol, a-lapachone, P-lapachone and their derivatives. 

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... 

There are also natural products of the 3,4-dehydro series (314). 3-Methyl-314 was isolated from heartwood of Paratecoma peroba (68N38), and the 2,2-dimethyl derivative (310, R = H) from wood of Rademachera sinica (81JCS(P1)2764). The last compound (dehydro-a-lapachone) was obtained also from isolapachol and DDQ 311 is formed first and then isomerized to 310 in the presence of acid (62MI1 69JOC120 78CJC517). 

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