Nanaomycin regioselective

Nanaomycin A 103 and deoxyfrenolicin 108 are members of a group of naphthoquinone antibiotics based on the isochroman skeleton. The therapeutic potential of these natural products has attracted considerable attention, and different approaches towards their synthesis have been reported [65,66]. The key step in the total synthesis of racemic nanaomycin A 103 is the chemo-and regioselective benzannulation reaction of carbene complex 101 and allylacety-lene 100 to give allyl-substituted naphthoquinone 102 after oxidative workup in 52% yield [65] (Scheme 47). The allyl functionality is crucial for a subsequent intramolecular alkoxycarbonylation to build up the isochroman structure. However, modest yields and the long sequence required to introduce the... 

This reaction is applied to the intramolecular regioselective cyclization of the 3-alkoxybenzoeyelobutenedione 60 to 61, a precursor of nanaomycin A 62 [33], (Scheme 23)... 

This regioselective synthesis of benzannelated rings, which, unlike its Friedel Crafts equivalent, is not perturbed by the nature of other directing groups carried by the ring, has been used in several syntheses. Indanone 76 from cyclisation of 75 is an intermediate in a synthesis of nanaomycin A,44 and tetralone 77 is an intermediate in a synthetic study towards daunomycin 45... 

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