Lapachol synthesis

A two-step transformation of conjugated dienes into non-conjugated ones was proposed for the synthesis of the difficult to-obtain lapachol (355) (a member of a class of antimalarial agents having an activity against the Walker carcinosarcoma 256) from the more available isolapachol 352183. This method consists in an oxidative cyclization of isolapachol 352 by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) to form a mixture of the products 353 and 354 (equation 127). Treatment of this mixture with dilute acid in... 

Complexes of lapachol with diverse metals like copper (II), iron (II), iron (III), chromium (III), aluminium (IE), yttrium (El), samarium (IE), gadolinium (IE), and dysprosium (IE) have been investigated [141-144]. Direct electrochemical synthesis of some metal derivatives of lapachol have been carried out [145]. Several P-lapachone hydrazo compounds were synthesized and characterized using spectroscopic techniques including X-ray analyses [146]. Selective aromatic reduction in pyranonaphthoquinones has also been reported [147-148]. 

A synthesis of lapachol using reaction conditions better than those used by Fieser was carried out by Fridman et al [149].They used the lithium salt of 2-hydroxy-1,4-naphthoquinone prepared in situ instead of the silver salt used for Fieser [150]. The lithium salt was prepared in situ by addition of lithium hydride to the frozen solution of the quinone in dimethyl sulfoxide, Fig. (14). As the solution thawed, the lithium quinone was slowly formed and was then alkylated with 3,3-dimethylallyl bromide. Lapachol was thus obtained in 40% yield. 

Lapachol occurs in the grain of some woods, including the South American lapacho. This yellow material can be prepared, in vitro, by the sequence shown below. Suggest a mechanism for this synthesis and for the interconversions of lapachol and a- and 3-lapachone. Which of the latter two is more stable How would you rationalize this ... 

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