Cobryketone Derived from Vitamin B₁₂via Palladium-Catalyzed Cleavage of the sp³–sp³ Carbon–Carbon Bond

Abstract

Heptamethyl cobyrinate was transformed into hexamethyl 8-nor-cobyrinate. The crucial step involved the synthesis of new, vitamin B12 derived cobryketone via palladium-catalyzed cleavage of the sp(3)-sp(3) carbon-carbon bond with the liberation of the ketone. The replacement of sp(3) carbon atom with sp(2) (C═O) at the 8-position produces a bathochromic shift of all absorption bands and makes α and β bands equal as a consequence of the expansion of the existing conjugated system of double bonds.

Small Alterations in Cobinamide Structure Considerably Influence sGC Activation

“…Substituents at c ‐ and d ‐positions are perhaps the easiest to modify, and their alteration represents a useful means for functionalization of cobalamin derivatives 15–17. Our research group recently developed a method for removal of the d side chain from heptamethyl cobyrinate ( 1 ) 18. Palladium‐catalyzed cleavage transforms 1 into cobryketone 3 , which, upon reduction with zinc powder, furnishes 8‐ nor ‐ c ‐acid 4 .…”

“…Compound 5 was synthesized according to the procedure published in ref. 18. Heptamethyl cobyrinate 1 was obtained from vitamin B 12 22…”

“…Preparation of amide 18 . Following the reported procedure,18 product 18 was isolated as a purple solid (19 mg, 63 %): R f =0.55 (EtOH/CH 2 Cl 2 10 %); mp: 125 °C; 1 H NMR (500 MHz, [D 6 ]acetone): δ =6.79 (t, J =5.1 Hz, 1 H), 5.82 (s, 1 H), 3.94 (d, J =9.0 Hz, 1 H), 3.75–3.73 (m, 4 H), 3.69–3.65 (m, 13 H), 3.56 (s, 3 H), 3.45 (t, J =5.1, 1 H), 3.37 (t, J =5.7, 2 H), 3.21 (t, J =5.0 Hz, 1 H), 3.12–3.04 (m, 2 H), 2.91–2.79 (m, 3 H), 2.71–2.64 (m, 2 H), 2.62–2.42 (m, 6 H), 2.35–2.29 (m, 4 H), 2.28–2.07 (m, 10 H), 1.97–1.81 (m, 4 H), 1.66 (s, 3 H), 1.50 (s, 3 H), 1.46 (s, 3 H), 1.41 (s, 3 H), 1.31 (s, 3 H), 1.16 ppm (s, 3 H); 13 C NMR (125 MHz, [D 6 ]acetone): δ =177.3, 176.7, 176.5, 174.2, 173.5, 173.2, 173.1, 173.0, 172.7, 171.4, 164.5, 163.9, 104.6, 103.3, 91.7, 83.7, 75.6, 62.0, 61.9, 59.1, 57.7, 55.9, 54.2, 52.5, 52.0, 51.94, 51.91, 51.8, 51.7, 48.9, 47.4, 46.6, 43.09, 43.06, 42.9, 41.9, 40.3, 34.2, 33.0, 32.8, 32.3, 32.0, 31.4, 31.2, 30.3, 30.1, 30.0, 29.8, 29.7, 29.5, 29.3, 28.8, 26.3, 25.5, 23.3, 22.6, 19.7, 19.4 ppm; UV/Vis (CH 2 Cl 2 ): λ max (ε)=589 (1.00×10 4 ), 547 (8.48×10 3 ), 371 (2.60×10 4 ), 315 (9.13×10 3 ), 229 nm (3.35×10 4 ); HRMS‐ESI ( m / z ) [ M +Na] + calcd for C 55 H 76 CoN 7 O 14 Na: 1140.4680, found: 1140.4703; Anal. calcd for C 55 H 76 CoN 7 O 14 : C 59.08, H 6.85, N 8.77, found: C 58.79, H 6.81, N 8.63.…”

Serendipitous synthetic entrée to tetradehydro analogues of cobalamins

“…12,13 A more recent synthetic strategy to gain access to B 12 -like architectures entails semisynthesis, which has focused particularly on modification of the macrocycle side chains. 14,15 Yet, the semisynthetic approach is somewhat limited by the rich array of functionalities arrayed about the perimeter of the B 12 macrocycle.…”

Csp3–Csp3Bond Cleavage in the Palladium-Catalyzed Aminohydroxylation of Allylic Hydrazones Using Atmospheric Oxygen as the Sole Oxidant

“…Accordingly, it has attracted tremendous attention among synthetic chemists. Various transition metals such as rhodium complexes or palladium complexes have been shown to be efficient catalysts for C–C bond cleavage. − Common strategies employed the use of a decarboxylation strategy or the use of special latent groups such as tertiary alcohol. Both these strategies have limitations in terms of substrate scope, working only for substrates which can ensure facile retro processes.…”