Synfacts 2021; 17(06): 0705
DOI: 10.1055/s-0040-1719754
Chemistry in Medicine and Biology

The Woodwardian Synthesis of Erythromycin A

Rezensent(en):
Dirk Trauner
,
Klaus-Peter Ruehmann
Woodward RB. * et al. Harvard University, Cambridge, USA
Asymmetric Total Synthesis of Erythromycin.

J. Am. Chem. Soc. 1981;
103: 3210-3213
DOI: 10.1021/ja00401a049.
Woodward RB. * et al.
J. Am. Chem. Soc. 1981;
103: 3213-3215
DOI: 10.1021/ja00401a050.
Woodward RB. * et al.
J. Am. Chem. Soc. 1981;
103: 3215-3217
DOI: 10.1021/ja00401a051.
 

Significance

Erythromycin A and its various macrolide analogues have been identified as potent broad-spectrum antibiotics that disrupt protein synthesis by blocking the bacterial ribosome. This promising therapeutic value, along with the structural challenge of the molecule, quickly attracted the attention of the synthesis community after its isolation in 1949. In 1956, R. B. Woodward stated that ‘Erythromycin, with all of our advantages, looks at present quite hopelessly complicated, particularly in view of its plethora of asymmetric centers.’ 25 years later his research group disclosed the first complete synthesis of erythromycin A, just about two years after Woodward had passed away.


#

Comment

One of the key insights of Woodward was identifying the similarity between the C3 to C8- and the C9 to C13-fragments and using dithiadecaline A as a common precursor. The rigidity of the ring system allowed for the stereoselectivity of multiple operations before it was desulfurized under Raney-nickel conditions. Interestingly, macrolactonization required the conformational bias of a cyclic acetal and carbamate. Glycosylation of the fully functionalized macrolactone with d-desosamine and l-cladinose occurred site- and stereoselectively.


#
#

Publikationsverlauf

Publikationsdatum:
18. Mai 2021 (online)

© 2021. Thieme. All rights reserved

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany