THE BIOSYNTHESIS OF HYOSCYAMINE - THE PROCESS BY WHICH LITTORINE REARRANGES TO HYOSCYAMINE

The incorporation of isotope from specifically-labelled 3-phenyllactic acid 4 or littorine 7 into 3 alpha-phenylacetoxytropane 10, 3 alpha-p henylacetoxy-6 beta,7 beta-epoxytropane and 3 alpha-(2'-hydroxyacetoxy )tropane 9 has been demonstrated. Transformed root cultures of Datura stramonium or Brugmansia (Datura) candida x B. aurea incorporated fed (RS)-3-phenyl[1,3-C-13(2),]lactic acid 4 into 3 alpha-phenylacetoxytro pane 10 and 3 alpha-phenylacetoxy-6 beta,7 beta-epoxytropane with the efficient retention of both C-13 nuclei. In contrast, no label was inc orporated into these two compounds from (RS)-3-phenyl[2-C-13,2-H-2] la ctate 4. From this evidence it can be deduced that 3-phenyllactic acid 4 is not incorporated into 3 alpha-phenylacetoxytropane 10 via free p henylacetic acid 6, a route which would result in the loss of the C-1 of 3-phenyllactic acid 4. Furthermore, henyl[1',3'-C-13(2)][actoyl)[me thyl-H-2(3)]tropine (littorine 7) was incorporated into 3 alpha-phenyl acetoxytropane 10, at up to 4% specific incorporation, with the retent ion of all the C-13 and H-2 nuclei. Label was also incorporated into 3 alpha-(2'-hydroxyacetoxy)tropane 9 from (RS)-3-phenyl[1,3-C-13(2)]lac tic acid 4 and phenyl[1',3'C-13(2)]lactoyl)[methyl-H-2(3)]tropine 7. W e propose, on the basis of these observations, a putative process for the rearrangement of littorine 7 to hyoscyamine 8 and suggest that bot h 3 alpha-phenylacetoxytropane 10 and 3 alpha-(2'-hydroxyacetoxy)tropa ne 9 arise as by-products of the rearrangement process.