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Total Synthesis and NMR Investigations of Cylindramide
Author(s) -
Cramer Nicolai,
Buchweitz Maria,
Laschat Sabine,
Frey Wolfgang,
Baro Angelika,
Mathieu Daniel,
Richter Christian,
Schwalbe Harald
Publication year - 2006
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.200501274
Subject(s) - sonogashira coupling , chemistry , wittig reaction , enantiopure drug , stereochemistry , dihydroxylation , pentalene , derivative (finance) , total synthesis , organic chemistry , enantioselective synthesis , molecule , palladium , financial economics , economics , catalysis
Cylindramide ( 1 ) was built up from three components: a hydroxyornithine derivative 7 , a tetrazolylsulfone 8 , and a substituted pentalene subunit 9 . Derivative 7 was prepared in a six‐step reaction sequence involving the Wittig reaction and a Sharpless asymmetric dihydroxylation starting from N ‐Boc‐3‐aminopropanal ( 12 ). Tetrazolylsulfone 8 was accessible in four steps from dioxinone 22 . The synthesis of the pentalene fragment 9 started from cycloocta‐1,5‐diene 26 , that was converted into enantiopure bicyclo[3.3.0]octanedione 29 . The latter was functionalized to give derivative 9 . The total synthesis was accomplished by inducing CC bond formation by Sonogashira coupling of derivatives 9 and 7 followed by olefination with tetrazolylsulfone 8 under Julia–Kocienski conditions, macrocyclization, and subsequent Lacey–Dieckmann condensation to form the tetramic acid unit. As indicated by extensive 1 H and 13 C NMR spectroscopic investigations (DQF‐COSY, ROESY spectra), the stereochemistry of synthetic cylindramide ( 1 ) corresponds with that of the naturally occurring product. ROE data were used for molecular modeling of the lowest‐energy structures for cylindramide.