Alpha‐ and Beta‐Diastereoisomers of Phenylcobalamin from Cobalt‐Arylation with Diphenyliodonium Chloride

Abstract

Organometallic aryl-cobalamins are B -derivatives featuring properties of potential 'B antivitamins'. Herein, we describe a new method for the preparation of aryl-cobalamins using versatile diaryliodonium salts as arylation agents. Formate or sodium borohydride reduction of aquocobalamin in presence of diphenyliodonium chloride furnished Co -phenyl-cobalamin PhCbl in a roughly 3:1 to 1:1 ratio with its coordination isomer αPhCbl, a first representative 'base-off' Co -aryl-cobalamin. The new structures were secured by detailed spectroscopic analysis, supplemented by an X-ray crystal structure analysis of PhCbl. Both types of coordination isomers of the aryl-cobalamins promise to be useful molecular tools in biomedical and biological studies.

Synthetic Approaches toward Vitamin B12 Conjugates

“…Reductive conditions are also suitable for the synthesis of arylcobalamins. Kräutler and co‐workers developed a methodology leading to these compounds involving the reduction of (H 2 O)Cbl ( 1 d ) to Co(II) with sodium formate and subsequent reaction with aryl diazonium salts ,. The resulting arylcobalamins were found to be light‐sensitive, which is consistent with the typical photosensitivity of alkylcobalamins.…”

Antivitamins B12 in a Microdrop: The Excited-State Structure of a Precious Sample Using Transient Polarized X-ray Absorption Near-Edge Structure

“…Antivitamins B 12 are a class of robust structural B 12 mimics that resist metabolic conversion into B 12 -cofactors and are capable of inhibiting vitamin B 12 activity. − Two antivitamins B 12 were previously studied with UV–visible transient absorbance spectroscopy . The phenyl-ethynylcobalamin (PhEtyCbl, Figure ) antivitamin is photostable with internal conversion to the ground state on a ca.…”

Functionalisation of vitamin B12 derivatives with a cobalt β-phenyl ligand boosters antimetabolite activity in bacteria

“…34 (s, HC2N), 7.26 (s, HC7N), 6.81 (d, J ¼ 5.7 Hz, HC4L), 6.76 (t, J ¼ 6.9 Hz, HC3L, HC5L), 6.66 (s, HC4N), 6.29 (d, J ¼ 3.1 Hz, HCR1), 5.89 (s, HC10), 5.79 (d, J ¼ 7.8 Hz, HC2L, HC6L), 4.70 (td, J ¼ 8.4, 4.3 Hz, HC3R), 4.42-4.33 (m, HC176), 4.30 (t, J ¼ 3.7 Hz, HC2R), 4.20 (d, J ¼ 8.4 Hz, HC3), 4.18-4.13 (m, HC4R), 3.97 (dd, J ¼ 12.9, 2.5 Hz, H a of H 2 C5R), 3.78 (dd, J ¼ 13.0, 4.2 Hz, H b of H 2 C5R), 3.57 (dt, J ¼ 14.0, 2.3 Hz, H a of H 2 C175), 3.43 (d, J ¼ 10.3 Hz, HC13), 3.36 (d, 10.0 Hz, HC19), Assignments were made based on 2D NMR studies (DQF-COSY, HSQC, HMBC, NOESY) and comparison with data from lit. 13 10-Bromo-Co b -cyanocobalamin (5). C10-bromination of 1 was performed based on a procedure published earlier by our group.…”

“…9,10 Syntheses, isolation, and characterization of the two novel doubly-modied derivatives 4 and 7 and four singly-modied Cbls (2, 3, 5 and 6) are described in more detail below and in the Experimental section. In this section, we outline only the 13 For the synthesis of 10-bromo-Co b -phenylcobalamin (7; Scheme 2 bottom), we considered that Cbls bearing good leaving groups are prone towards reducing agents. Therefore, 10-bromo-Co b -cyanocobalamin ( 5) is not compatible with arylation conditions using NaBH 4 .…”

“…Cary 50 Scan spectrophotometer (Varian) or Specord 250 Plus (Analytik Jena) using 1 cm quartz cuvettes (Hellma Analytics); l max (log 3) in nm. Both 1 H-and 13 C-NMR spectra were carried out at 298 K in D 2 O or CD 3 OD and at 500 MHz or 126 MHz, respectively. The 1 H-NMR spectra were performed in an AVANCE NEO 500 MHz spectrometer (Bruker) using a 5 mm-z-gradient RT-BBI probehead; d in ppm relative to HDO (d 4.79; corresponds to TMS (d 0.00)) or CHD 2 OD (d 3.31; corresponds to TMS (d 0.00)), J in Hz.…”