Aufbau der Ligandsysteme des C, D‐Tetradehydrocorrins und Isobakteriochlorins durch Sulfidkontraktion. Kurzmitteilung

Ofner, Silvio; Rasetti, Vittorio; Zehnder, Beat; Eschenmoser, Albert

doi:10.1002/hlca.19810640520

Cited by 36 publications

(10 citation statements)

References 64 publications

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“…[54] That the fourth methyl group to be attached to the macrocycle appears at C-I 7 in precorrin-4 (31) is in satisfying agreement with the the results of pulse-labeling studies, outlined earlier, on the order of the C-methylations after the third one. In both Pr.…”

Section: Me41supporting

confidence: 80%

Vitamin B₁₂: How the Problem of Its Biosynthesis Was Solved

Blanche

Cameron

Crouzet

et al. 1995

Angew. Chem. Int. Ed. Engl.

145

108

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Vitamin B,, is an essential vitamin for human health, and lack of it leads to pernicious anemia. This biological activity has attracted intense interest for some time; in addition, the complex architecture of the B,, molecule has fascinated chemists and biochemists since its discovery as the first natural organocobalt complex and the establishment of its structure by X-ray analysis. The organic ligand surrounding the cobalt displays many stereogenic centers along its periphery carrying reactive functional groups. This complexity led vitamin B,, to be rightly regarded as an extreme challenge to the synthetic chemist. Yet microorganisms achieve this synthesis in vivo with complete control of regio-and stereochemistry. How do they do it? This review tells the full remarkable story. Success in unraveling this biosynthetic puzzle resulted from a collaborative effort by biologists and chemists using the full range of methods available from their disciplines-from genetics at one end of the spectrum to synthesis and NMR spectroscopy at the other. This work can act as a guide for future research on the biosynthesis of yet more complex natural substances.

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Section: Me41supporting

confidence: 80%

Vitamin B₁₂: How the Problem of Its Biosynthesis Was Solved

Blanche

Cameron

Crouzet

et al. 1995

Angew. Chem. Int. Ed. Engl.

145

108

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“…The biosynthesis of factor IV may indeed involve just such a cyclopropane intermediate (Scheme I), which subsequently loses C-20 as acetaldehyde (3 acetic acid), thereby reviving one of the earliest concepts for ring contraction. Several alternatives remain, including proton catalyzed ring closure of a seco-corrinoid (18,19). Thus, in cobalt precorrin-4 (Scheme II) the ring contraction is orchestrated not by molecular oxygen, but by internal delivery of oxygen functionality that in turn could be mediated by remote interaction of cobalt with the carboxylate function in ring A and͞or addition of the fourth C-methyl group in ring D at position 17 or 18.…”

Section: Resultsmentioning

confidence: 99%

Biosynthesis of vitamin B ₁₂ : Factor IV, a new intermediate in the anaerobic pathway

Wang

et al. 1996

Proc. Natl. Acad. Sci. U.S.A.

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The structure of a novel tetradehydrocorrin, factor IV, isolated from Propionibacterium shermanii has been established by multidimensional NMR spectroscopy. Incorporation of radiolabeled factor IV into cobyrinic acid established the biointermediacy of this cobalt complex, whose structure has implications for the mechanisms of the anaerobic pathway to B 12 .In the aerobic bacterium Pseudomonas denitrificans, the biosynthetic pathway to vitamin B 12 , featuring an oxygenrequiring step, has been established (for reviews, see refs. 1 and 2), but it is now clear that a second, anaerobic route to corrin has existed in nature for ca. 4 billion years (2, 3). Thus, the obligate anaerobes, such as methanogenic bacteria, and the semianaerobic Propionibacterium shermanii are able to synthesize B 12 by processes that differ at several pivotal steps from the aerobic pathway. The Ps. denitrificans route uses a twostage ring contraction sequence on the metal-free substrate precorrin-3, using O 2 (4) to fashion ␥-lactone and tertiary hydroxyl functions at C-1 and C-20 in precorrin-3x (Scheme I) as a prelude to a pinacol-like rearrangement, whereas cobalt is inserted late, i.e., not until all S-adenosylmethionine (AdoMet)-derived methyl groups are in place and amidation of the carboxylates has begun (1, 2).In contrast, it has been found (5) that in Pr. shermanii cobalt is inserted early into precorrin-3, which is ring-contracted without O 2 as cofactor (Scheme I), and at a later, unknown stage, a unique exchange of carbonyl oxygen at the C-27 (ring A) acetate occurs (6, 7); this is another event that is not paralleled in aerobic metabolism (8). In this report, we describe the isolation of a new B 12 intermediate from Pr. shermanii whose surprising structure provides circumstantial but compelling evidence for those mechanisms operating during anaerobic biosynthesis that mediate ring contraction and loss of the 2-carbon fragment from the western side. MATERIALS AND METHODSPreparation of Factor IV from epi-Factor II. A cell-free extract of Pr. shermanii (from 50 g of wet cells) was prepared by sonication (50 min at 0-4ЊC) in phosphate buffer (pH 7.6; 50 ml). Glutathione (5 mg), ATP (22 mg), NAD (5 mg), NADH (10 mg), AdoMet (75 mol), EDTA (3.5 mol), Co 2ϩ (4 mol), and Co 3ϩ (1.8 mol) were added to the supernatant of the centrifuged suspension (17,000 ϫ g; 25 min at OЊC). For preparative isolation, 3-epi; 8-epi factor II ( Fig. 1; 500 mol) was added, and the incubation was carried out at 31ЊC for 16 hr. Sodium cyanide (5 mg) was then added, and the tetrapyrrolic mixture was adsorbed on DEAE-Sephadex A-25 (Pharmacia) followed by extraction and esterification by MeOH͞

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“…Der Schmelzpunkt 155 -157°C fur rac-2 stimmt gut mit dem von Battersby') fur rac-2 angegebenen Wert (154-156°C) uberein, liegt aber erwartungsgemaB unter dem Wert fur ,,naturliches" Z5) (164-165 "C 27 (s, 3H, 3-CH3 (5), 97 (41 96 (15), 95 (17), 94 (20), 82 (4), 81 (18), 80 (21), 79 (7), 68 (6), 67 (18) (12), 267 (27) 227 (4, 213 (9), 199 (9), 91 (100) C 60.49 H 7.61 N 11.76 Gef. C 60.33 H 7.57 N 11.63 (3SJR) -5-Cyan-4,4,5-trimethyl-2-thioxopyrrolidin-3-propionsaure-methylester (36) Brommalonsaure-allylester-tert-butylester (rac-39): Zu 1.7 ml (1.41 g, 10 mmol) N-Isopropylcyclohexylamin in 10 ml wasserfreiem Tetrahydrofuran lieD man bei -40°C unter Argon 5.9 ml (1.7 M in Hexan, 10 mmol) n-Butyllithium zutropfen. Nach 30min.…”

Section: Synthese Von Bonellin-dimethylester (Vac-2 B) Uber Den Lineaunclassified

Totalsynthese von (±)‐Bonellin‐dimethylester

Montforts

Schwartz

1991

Liebigs Ann. Chem.

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Aufbau der Ligandsysteme des C, D‐Tetradehydrocorrins und Isobakteriochlorins durch Sulfidkontraktion. Kurzmitteilung

Abstract: Professor George Biichi zurn 60. Geburtstag gewidmet

Cited by 36 publications

References 64 publications

Vitamin B₁₂: How the Problem of Its Biosynthesis Was Solved

Vitamin B₁₂: How the Problem of Its Biosynthesis Was Solved

Biosynthesis of vitamin B ₁₂ : Factor IV, a new intermediate in the anaerobic pathway

Totalsynthese von (±)‐Bonellin‐dimethylester

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Aufbau der Ligandsysteme des C, D‐Tetradehydrocorrins und Isobakteriochlorins durch Sulfidkontraktion. Kurzmitteilung

Abstract: Professor George Biichi zurn 60. Geburtstag gewidmet

Cited by 36 publications

References 64 publications

Vitamin B12: How the Problem of Its Biosynthesis Was Solved

Vitamin B12: How the Problem of Its Biosynthesis Was Solved

Biosynthesis of vitamin B 12 : Factor IV, a new intermediate in the anaerobic pathway

Totalsynthese von (±)‐Bonellin‐dimethylester

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Vitamin B₁₂: How the Problem of Its Biosynthesis Was Solved

Vitamin B₁₂: How the Problem of Its Biosynthesis Was Solved

Biosynthesis of vitamin B ₁₂ : Factor IV, a new intermediate in the anaerobic pathway