N-Boc Deprotection and Isolation Method for Water-Soluble Zwitterionic Compounds

Abstract

A highly efficient TMSI-mediated deprotection and direct isolation method to obtain zwitterionic compounds from the corresponding N-Boc derivatives has been developed. This method has been demonstrated in the final deprotection/isolation of the β-lactamase inhibitor MK-7655 as a part of its manufacturing process. Further application of this process toward other zwitterionic compounds, such as dipeptides and tripeptides, has been successfully developed. Furthermore, a catalytic version of this transformation has been demonstrated in the presence of BSA or BSTFA.

Mild deprotection of the N-tert-butyloxycarbonyl (N-Boc) group using oxalyl chloride

“…These include N-Boc deprotection via thermolysis 31,32 and TMSI-mediated deprotection of N-Boc in zwitterionic compounds. 33 In most cases, small molecules with sensitive functional groups or unique scaffolds are not compatible with these harsh deprotection conditions. Therefore, alternative reagents for deprotection, while providing functional group tolerance will be quintessential in the masking and unmasking of aminesa paradigm for broad utility.…”

Hepatoprotective Principles and Other Chemical Constituents from the Mycelium of Phellinus linteus

“…In addition to phellinulins A–N ( 1 – 14 ), nineteen known compounds, including phellilins A–C ( 15 – 17 ) [ 29 ], γ-ionylideneacetic acid ( 18 ) [ 28 ], ergosta-(7,9(11),22t)-trien-3β-ol [ 30 ], (−)-cinnamolide [ 31 ], ergosterol peroxide [ 32 ], 6β-hydroxycinnamolide [ 33 ], cinnamolide-3β-ol [ 34 ], 5-hydroxy-4-phenyl-5 H -furan-2-one [ 35 ], p -hydroxybenzaldehyde [ 36 ], lumichrome [ 37 ], phenylalanine-leucine [ 38 ], phenylalanine-isoleucine [ 39 ], phenylalanine [ 40 ], proline-valine [ 41 ], phenylalanine-proline [ 42 ], proline-leucine [ 43 ] and phenylalanine-alalinine [ 44 ] were also identified by comparison of their physical and spectroscopic data with those reported.…”

Peptide‐Chain Elongation Using Unprotected Amino Acids in a Micro‐Flow Reactor

“…The resultant mixture was passed through a reaction tube (inner diameter: 0.800 mm, length: 531 mm, volume 267 μL, reaction time: 5.00 s) at the same temperature. Then, the resultant mixture and a solution of H‐ l ‐Phe‐Gly‐ONa ( 3 f ) (0.340 m , 1.70 equiv) in H 2 O (flow rate: 2.00 mL min −1 ) were introduced to the V‐shape mixer at 20 °C. The resultant mixture was passed through a reaction tube (inner diameter: 0.800 mm, length 1724 mm, volume: 867 μL, reaction time 10.0 s) at the same temperature.…”