Synthesen von Gallenfarbstoffen, VI: Totalsynthese des (+)(4R,16R)‐ und (−)(4R,16S)‐[18‐Vinyl]mesourobilin IXα‐dimethylesters

Abstract

Racem. methyl 5'-tert-butoxycarbonyl-[4-vinyl]isoneobilirubinate (7a) has been synthesized by oxidation of the 5(2H)-dipyrrylmethanone-~elenide 5m with hydrogen peroxide and subsequent thermal decomposition of the formed selenoxide. The corresponding 5'-formyl derivative 7b was condensed with the known ( +)(R)-5'-carboxyneobilirubinic acid (6a) yielding, after esterification with diazomethane, the two diastereomeric (+)(4R,16R)-and ( -)(4R,16S)-[ 18-vinyl]-mesourobilin IXa dimethyl esters (8a and Sb, respectively) which were for the first time fully characterized on the basis of their CD, ORD, 'H-NMR, UV/VIS, and mass spectra. In the course of this work 4-methy1-3-vinyl-3-pyrrolin-2-one (3) was prepared in 20% yield from 2b. Als Urobiline (1,4,5,15,16,19,21,24-0ctahydro-1,19-dioxo-22H-biline

Synthesis of bile pigments. 9. Chemical total synthesis of (+)-(2R,16R)- and (+)-(2S,16R)-phycoerythrobilin dimethyl ester

“…A solution of the foregoing aldehyde (1 g) and 3-(2-hydroxyethyl)-4-methyl-3-pyrrolin-2-one15 (360 mg) in a mixture of methanol (30 mL) and 4 N aqueous KOH (30 mL) was stirred for 14 h at room temperature. The crude product which was isolated according to the procedure described in ref 15 for the corresponding 5'-tert-butyl ester was purified by chromatography on silica gel eluting with methylene chloride/methanol (96:4) to yield 1 g (75%) of 10; mp 160 °C (from methylene chloride/n-hexane): [a]25o -108.8°( 2.6 g/L in methanol); ORD (87 mg/L in methanol) [M] 600 (-540), 432 (-3000), 374 nm (0°); IR (KBr) 3330, 2900, 1740, 1670, 1440, 1280cm"1; NMR (90 MHz) 0.99 (3 H) and 1.07 (6 H) (each s, l"and 3"-CH3), 1.3-1.8 (m, 7 H, fenchyl-CH2 and 4"-H), 1.50 (s, 2"-CH3), 2.11 (s, 6H, 3-and 3'-CH3), 2.4-2.9 (m, 4 H, a-CH2 of propionic ester and C/f2CH2OH), 3.11 (t, J = 8 Hz, /3-CH2 of propionic ester), 3.4-4.0 (m, 3 H, CH2OH and OH), 3.67 (s, OCH3), 5.98 (s, methine ), 8.71 and 8.86 (each br s, NH); MS m/e (rel intensity) 512 (< 1) M+, 362 (<1) M+ -1-methylcamphene. 318 (100), 362 -C02, 287 (95), 318 -OCH3.…”

“…Owing to the fact that 5'-hydroxycarbonylisoneobilirubinic acid {rae-15, ethyl instead of vinyl) could be resolved in its antipodes by fractional crystallization of their corresponding salts with optical active bases,17 we intended to carry out a separation of the racemic mixture of 15 by the same procedure. However, our attempts to liberate the carboxylic acid group at C-5' by alkaline hydrolysis of the dimethyl ester rae-1618 failed; the reaction product was 5'hydroxycarbonylisoneoxanthobilirubinic acid (26), which was probably formed by migration of the vinylic double bond of 15 into the methylene bridge. On the other hand, cleavage of isobutene from the tert-butyl ester rae-1718 by means of cold trifluoroacetic acid was accompanied by decarboxylation, thus yielding the corresponding methyl (±)- [4-vinyl]isoenobilirubinate (rae-18)16 instead of the desired S'-hydroxycarbonyl derivative.…”

“…of a sample of (+)-(47?,16R)-[l 8-vinyl] mesourobilin IXa dimethyl ester synthesized earlier by us by an independent route 15. …”

“…After decolorization was complete, the solvent was removed under reduced pressure and the residue was treated with a solution made from the above mixture of mesylates (240 mg) in tetrahydrofuran (80 mL). The mixture was stirred for 20 min at room temperature and then worked up as described in ref15 for the corresponding S'-tert-butyl ester, yielding 30 mg of starting material and 148 mg (52%) of 13 as a mixture of epimers at C-2. By fractional crystallization of the latter from ether, 70 mg of dextrorotatory 13a was obtained: mp 139-140…”