MODEL EXPERIMENTS ON BILE PIGMENT FORMATION 



457 



verdin (1676); cf. Chapter IV, Section 3.2.1. Similarly, pyridine 

 mesohemochrome was shown to be transformed into the correspond- 

 ing mesobiliverdin compound, the "ferrobilin" of Fischer and his 

 collaborators (803). 



H H 



porphyrin biliverdin bilirubin 



Fig. 1. Relationship of biliverdin and bilirubin to porphyrin. 



It has been shown in Chapter IV that these compounds do not 

 contain their iron in complex combination with the tetrapyrrolic 

 system. By neutralization they are easily converted into biliverdins. 

 In fact, they are formed only under the conditions of the acid esteri- 

 fication and would not be stable under physiological conditions. 



In this way pure crystalline bile pigments were first obtained from 

 hematin compounds in a reaction which could be considered as a 

 model of their formation from hemoglobin in the animal body.* 

 Since hemin had been synthesized by Fischer (cf. Chapter III), the 

 total synthesis of the bile pigments had also been achieved. f 



* The significance of these experiments was overlooked for several years. For 

 example, Watson, in his contribution to Downey's Handbook- of Hematology, published 

 in 19.'58 iS9S9), still discussed only the old theory which assumed that hemoglobin is 

 transformed into bilirubin with hematin and porphyrin as intermediate products; 

 Lemberg's 19.S5 paper is not mentioned; cf. also Fischer (SGI, p. 628). In 1938 Fischer 

 and Libowitzky (.S\J6"), transforming coprohemin into coprobiliverdin by coupled 

 oxidation with ascorbic acid, claimed: '"Damit ist . . . ziim ersten Male mit guter Aus- 

 beut-e auj einem Wege wie er in der leheiulen Zelle ohne weiferex denkhar i.st, in vilro aus 

 einem Haemin ein einheitlicher (iallenfarbstoff erhallen irorden." (Italics in original.) 

 In fact, their paper contained nothing new in principle. Crystalline l)ile pigments had 

 been obtained from hemins by Lembcrg in 19S5 ildSl), and the fact that ascorbic acid 

 could be used for this reaction had been known since the work of Karrcr and co-workers 

 in 1933 (U69). The verdohemochrome formation by coupled oxidation with ascorbic 

 acid had been carefully investigated by Leniberg and co-workers (l(iS7,lG9(>; cf. also 

 6If7,l(!2), who had shown that it could be carried out at physiological conditions of 

 pH and temperature. In the same year Lembcrg and co-workers transformed hemo- 

 globin into crystalline l)iliver(lin by coupled oxidation with ascorl)ic acid {1707). 



tStier {2i)r>r>) made the objection against this claim that a total synthesis should 

 also provide an unequivocal proof of the structure; in our opinion the term has no such 

 connotation. 



