Efficient Synthesis of Lactate‐Containing Depsipeptides by the Mitsunobu Reaction of Lactates

Abstract

The Mitsunobu reaction has been used as an efficient tool for the synthesis of orthogonallyprotected and unprotected depsipeptides such as Boc/Fmoc-l-Lys(Alloc)-d-Ala-d-Lac-OAllyl or l-Lysd-Ala-d-Lac that are bacterial cell wall precursor analogues found in vancomycin-resistant enterococci.

Apratyramide, a Marine-Derived Peptidic Stimulator of VEGF-A and Other Growth Factors with Potential Application in Wound Healing

“…The α-hydroxy carboxylic acid 4 was prepared from l -isoleucine by a published protocol . The esterification of N -Boc- O -Me-tyrosine with acid 4 provided ester 5 in 96% yield by Mitsunobu reaction (Ph 3 P/DEAD) . The Boc group of ester 5 was removed using 4 M HCl in ethyl acetate.…”

“…42 The esterification of N-Boc-O-Metyrosine with acid 4 provided ester 5 in 96% yield by Mitsunobu reaction (Ph 3 P/DEAD). 43 The Boc group of ester 5 was removed using 4 M HCl in ethyl acetate. Then, the desired N,N-dimethylated amino ester 2 was formed by a reductive alkylation reaction of the free amine in 5 using a mixture of aqueous HCHO and NaBH 3 CN.…”

Mitsunobu and Related Reactions: Advances and Applications

“…Due to the large number of other applications involving similar inversion/epimerization, we only list them here; the structural drawings pertaining to these references are given in the Supporting Information (Table S1). These pertain to the synthesis of (i) pregnanone derivatives, (ii) glucosphingolipids, (iii) pyrrolidine-amide oligonucleotide mimics, (iv) tubronic acid, (v) enantiopure butanoates, (vi) macroviracins, (vii) reduced products of cis - and trans -hexahydronaphthalenones, (viii) stereoinversion of myo -inositol into scyllo -inositol, (ix) orthogonally-protected and unprotected depsipeptides such as l -Lys- d -Ala- d -Lac and Boc-( S )-HOMeVal-( R )-Hmb, (x) (2 S ,3 S ,4 R )-4-( tert -butyldimethylsilyloxy)-2,3-isopropylidenedioxy-4-phenylbutanoate, (xi) dihydroxycholesterol, (xii) the acetate of the triol derived from jasminine, (xiii) stereochemically inverted products of xylofuranosyl derivatives, (xiv) 6- epi- aucubin, (xv) hydroxyethylene dipeptide isosteres (e.g. L-682,679), (xvi) orobanchol (a germination stimulant), (xvii) long chain pentadeca-1,3,5,7,9,11,13,15-octols (16 diastereomers), (xviii) mycalamide A (natural product), (xix) murisolin (natural product), (xx) leucascandrolide A (natural product with a sterically congested carbon), , (xxi) l -lyxose esters, (xxii) cryptophycin (5-hydroxy acid subunit), (xxiii) polycyclic carbohydrates, (xxiv) protected aminooxyprolines, (xxv) carbahexopyranose stereoisomers, (xxvi) deoxynucleic guanidine (DNG) oligonucleotide, (xxvii) D-hica, a component of kulokekahilide-2, (xxviii) methylsulfonate esters, (xxix) (4 R ,5 S )- and (4 S ,5 R )-muricatacins, (xxx) trioxilins, (xxxi) functionalized β-C-glycosyl aldehydes (a part of ambruticin), (xxxii) pyrrolidinols, (xxxiii) carbocyclic nucleosides, (xxxiv) Δ 2 -OPC-8:0 (a substituted cyclopentanone derivative), (xxxv) fluorescence-labeled probes based on phyllanthurinolactone [in these cases, 4-dimethylaminophenyldiphenylphosphine ( 2 ) instead of Ph 3 P worked better], (xxxvi) (+)-cardiobutanolide, (xxxvii) 3-amino-2,3,6-trideoxysugars, (xxxviii) sesquiterpene lactones, (xxxix) 3-methylcyclopentadecanol, (xl) optically active β-methyl-γ-alkyl-γ-butyrolactone, (xli) chiral P,N-ligands with a cyclohexane backbone, (xlii) optically active aminobenzindanol, (xliii) cyclopenta[ d ]pyridazinediol, (xliv) 4-hydroxytetrahydropyranone, (xlv) alkynic esters as precurso...…”