Total synthesis of hyacinthacines

The first total synthesis of hyacinthacine using sugar in the chiral pool strategy was reported by Martin et al. in 2001 (Scheme 1) and concerned (+)-hyacinthacine A2 [12]. The key step was a ring-closing metathesis of the suitable allylpyrrolidine II which allowed the formation of the B-ring of the pyrrolizidine. 

SCHEME 2 Total synthesis of hyacinthacine A2 according to Martin et al. 

In 2003, Goti et al. [13] described the total synthesis of hyacinthacine A2 through cycloaddition between acrylic acid derivatives and a carbohydrate-derived nitrone 31, which was obtained firom L-xylose or D-arabinose (Scheme 3). 

SCHEME 6 Total synthesis of hyacinthacine according to Goti et al. 

In 2005, Py and colleagues reported an efficient total synthesis of hyacinthacine A2 based on a Sml2-induced nitrone umpolung [19]. This elegant... 

The first total synthesis of (+)-hyacinthacine A3 was reported in 2002 starting from the pyrrolizidine XII which was further elaborated into the unsaturated ketone XIII (Scheme 17) [25]. 

Total Synthesis of Hyacinthacines from Nonchiral Pool Sources... 

While most of the syntheses of hyacinthacines are based on the modification and elaboration of precursors from the chiral pool, less effort has been directed toward the construction of the pyrrolizidine skeleton using non-natural precursors. This chapter summarizes racemic as well as enantioselective total synthesis of hyacinthacines reported to date, which start from nonchiral pool sources. In this context, biocatalysis constitutes the most widely used alternative to the chiral pool approach. Enzymatic kinetic resolution using lipases but also aldolase-mediated reactions have been successfully employed to provide precursors that were later elaborated toward hyacinthacines. Synthetic chiral auxiliaries have also been used successfully in this context. 

Delair et al. [44] recently devised an elegant approach toward hyacinthacine Al 6 using their sterically hindered homochiral benzyl alcohol Stericol 150 [45] (Scheme 42). [2+2]-Cycloaddition between a dichloroketene and an enol ether flanked by the chiral auxiliary XVlll was used as one of the key steps in the total synthesis of hyacinthacine Ai 6. The CH2OH moiety at C-3... 

SCHEME 43 Total synthesis of hyacinthacine Ai according to Delair et at. 

SCHEME 44 Total synthesis of hyacinthacine Bi according to Delair et al. 

SCHEME 46 Total synthesis of hyacinthacine B3 according to Pyne et al. 

SCHEME 52 Total synthesis of hyacinthacines Ae and A7 according to Donohoe et al. 

SCHEME 54 Total synthesis of hyacinthacine A2 accrading to Blechert el al. 

SCHEME 55 Total synthesis of hyacinthacine A2 accOTding to Blechrat et al. 

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