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Total Synthesis and Configurational Assignment of Chondramide A
Author(s) -
Schmauder Anke,
Sibley L. David,
Maier Martin E.
Publication year - 2010
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200903500
Subject(s) - chemistry , stereocenter , stereochemistry , dihydroxylation , depsipeptide , tripeptide , regioselectivity , mitsunobu reaction , derivative (finance) , amino acid , enantioselective synthesis , organic chemistry , catalysis , biochemistry , financial economics , economics
The first total synthesis of the cyclodepsipeptide chondramide A ( 2 b ) is described. This depsipeptide is composed of four subunits, namely L ‐alanine, N ‐Me‐ D ‐tryptophan, 3‐amino‐2‐methoxy‐propionic acid (β‐tyrosine derivative), and a 7‐hydroxy‐alkenoic acid. While the configuration of the stereogenic centers in the 7‐hydroxy‐alkenoic acid were known, the configuration of the tyrosine derivative required clarification and turned out to be (2 S ,3 R ) or (2 L ,3 L ), respectively. The synthesis of the 3‐amino‐2‐methoxy‐3‐arylpropanoic ester 20 b relied on an asymmetric dihydroxylation yielding diol ent ‐ 15 a followed by a regioselective Mitsunobu substitution leading to 3‐azido‐2‐hydroxypropanoate 18 b . We could also show that the ester bond in the seco compound 26 b can be fashioned by a Mitsunobu esterification by using hydroxy ester (7 S )‐ 7 and the tripeptide acid 25 b . This synthesis should allow for the preparation of various analogues.