Synthetic studies relevant to biosynthetic research on vitamin B12. Part 1. Syntheses of C-methylated chlorins based on 1-pyrrolines (3,4-dihydropyrroles)

Abstract

Two routes are explored for the synthesis of chlorins geminally substituted in the reduced ring; both involve cyclisations of 1 -pyrroline (3,4-dihydropyrrole) systems promoted by copper( 11) salts. In the preferred synthesis, a pyrrolomethyl-1 -pyrroline is combined with a 5-bromo-5'-bromomethylpyrromethene; though not high yielding, this approach involves few steps from readily prepared building blocks.

Refined Synthesis of 2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin, a Deceptively Simple Precursor to Hydroporphyrins

“…The organic layer was dried (Na 2 SO 4 ), concentrated and subjected to high vacuum to remove traces of isopropanol. The residue was dissolved in a small quantity of CH 2 Cl 2 and filtered through a silica pad (CH 2 Cl 2 ) to afford a pale yellow oil (0.106 g, 76%): 1 H NMR data were consistent with previously reported values; 2 1 H NMR δ 3.31 (t, J = 6.8 Hz, 2H), 4.60 (t, J = 6.8 Hz, 2H), 6.00-6.09 (m, 1H), 6.14-6.18 (m, 1H), 6 …”

“…HCOONH 4 (252 g, 3.90 mol) and zinc dust (261 g, 3.90 mol) were added and resulting suspension was vigorously stirred using a mechanical stirrer (see note iv below). After 2 h, GC analysis did not show any starting hexanone (5) or intermediate N-oxide (6). The mixture was filtered through filter paper and the filter cake was washed with ethyl acetate (2500 mL).…”

“…1 We recently developed rational syntheses of non-natural chlorins 2-4 (Scheme 1) and oxochlorins 5 by extending routes developed by Battersby for the synthesis of naturally occurring hydroporphyrins. 6 The synthesis entails reaction of an Eastern half (A) with a Western half (1) to form a tetrahydrobilene-a, which upon oxidative cyclization affords the zinc chlorin. The Eastern half is easily available.…”

Synthesis of hydrodipyrrins tailored for reactivity at the 1- and 9-positions

“…Three synthetic approaches to hydrodipyrrins that have been developed over the years include (1) stepwise synthesis beginning with a pyrrole-2-carboxaldehyde and proceeding via nitroaldol condensation, reduction, Michael addition and metal-mediated reductive cyclization; 16,17,20,22,23,30,49 (2) convergent synthesis utilizing a Wittig reaction of a pyrrole-derived phosphorus ylide and a thione; 21,24-26 and (3) palladium-mediated coupling of a halo-pyrrole with an ethynyl compound followed by cyclization. 27-29,50 The first method, while both the earliest and the most traditional of the three routes, has been exploited herein to gain access to a variety of hydrodipyrrin compounds.…”

“…16,17,[19][20][21][22][23][24][25][26][27][28][29] (By contrast, the tetrahydrodipyrrins prepared to date are fewer in number and typically contain the same α-substituents as those of 2. 23,24,30 ) The representative collection of dihydrodipyrrins (A-F) shown in Chart 2 illustrates the substituents at the pyrroline and pyrrole α-positions that have been employed to engender distinct nucleophilic or electrophilic reactivity features. The reactivity includes an electrophilic pyrrole (α-formyl: A ,27 B ,27 D , 20,21,[23][24][25][26], nucleophilic pyrrole (no α-substituent: C ;17 E 27 and F 27 upon decarboxylation), nucleophilic pyrroline (α-methyl, which forms an enamine: C, D), and electrophilic pyrroline via leaving groups (α-formyl: B, E; α-(thio)alkoxide: D, F; or α-triflate: F) or via an α-unsubstituted pyrroline Noxide 22 (not shown).…”