Advanced procedure for the enzymatic ring opening of unsaturated alicyclic β-lactams

A direct enzymatic method for the preparation of cyclic beta-lactams and beta-amino acids was recently developed, involving the Lipolase-catalyzed enantioselective hydrolysis of racemic beta-lactams in an organic solvent. Vibrational circular dichroism (VCD) spectroscopy combined with quantum chemical calculations at ab initio (DFT) level of theory has now been applied to determine the absolute configuration and conformation of a series of cyclic beta-lactams (1-10). The absolute configuration of 8 was derived from X-ray crystallography. Only indirect evidence was available for 1, 2, 5, 6, and 7. The absolute configuration of the new lactams 3, 4, 9, and 10 was not known previously. The VCD analysis indicated the homochirality of the studied lactams. The conformation of the flexible beta-lactams was also predicted from the VCD data. Even in the cases where multiple conformers are allowed, the predominance of one conformer was found, with the exception of 2, being present as a mixture of four conformers. Beta-lactams tend to form H-bonded dimers. The fine structure of the amide I VCD band suggested that only a small population of H-bonded dimers is formed in deuterated chloroform.

show abstract

“…Our , and 5-7 3,14 . The results confirmed the enantiopreference of Lipolase for the same set of compounds.…”

Section: Resultsmentioning

confidence: 72%

“…[1][2][3] High enantioselectivity (E > 200) was observed when the reactions were performed with 1 equivalent of water in diisopropyl ether at high temperature.…”

mentioning

confidence: 99%

VCD spectroscopic investigation of enantiopure cyclic β‐lactams obtained through lipolase‐catalyzed enantioselective ring‐opening reaction

et al. 2006

Self Cite

View full text Add to dashboard Cite

show abstract

“…Enantiomerically pure β-amino acid (-)-23 (Ͼ 98 % ee) [10] was prepared by the Lipolase-catalyzed (Lipase B from Candida antarctica) enantioselective ring cleavage of unsaturated racemic β-lactam 22. [11] High enantioselectivity (E Ͼ 200) was observed when the reaction was performed with 0.5 equiv. of H 2 O in iPr 2 O at 60°C.…”

Section: Resultsmentioning

confidence: 99%

Selective Synthesis of New Fluorinated Alicyclic β‐Amino Ester Stereoisomers

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…66 The medicinal chemistry route of CEP-28112 involved coupling three key structures, the benzocycloheptane unit (A-ring), the diaminopyrimidine central core (B-ring) and the bicyclic amino amide fragment (C-ring). Allwein and coworkers 16 described an efficient, scalable eight-step process for the preparation of CEP-28112 using CAL-B (Novozym 435) as catalyst in a stereoselective step 67,68 (MTBE with 1 equiv. of H 2 O, 50 °C) (Scheme 10).…”

Section: Cep-28112mentioning

confidence: 99%

Preparation of pharmaceutically important enantiomer components through lipase catalysed acylation and hydrolysis

Galla¹

View full text Add to dashboard Cite

Advanced procedure for the enzymatic ring opening of unsaturated alicyclic β-lactams

Cited by 69 publications

References 30 publications

VCD spectroscopic investigation of enantiopure cyclic β‐lactams obtained through lipolase‐catalyzed enantioselective ring‐opening reaction

VCD spectroscopic investigation of enantiopure cyclic β‐lactams obtained through lipolase‐catalyzed enantioselective ring‐opening reaction

Selective Synthesis of New Fluorinated Alicyclic β‐Amino Ester Stereoisomers

Preparation of pharmaceutically important enantiomer components through lipase catalysed acylation and hydrolysis

Contact Info

Product

Resources

About