Total synthesis of 1233A

Wovkulich, Peter M.; Shankaran, K.; Kiegiel, Katarzyna; Uskoković, Milan R.

doi:10.1021/jo00056a013

Cited by 99 publications

(25 citation statements)

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“…25 As a consequence, sialic acid poses a significant challenge, and glycal 4 is formed under various sialidation conditions. According to Wovkulich et al, 38 the dehydration pathway in the Mitsunobu 3 CN at À45°C, DEAD was added. The mixture was stirred for 10 min, then 1b was added, and stirring continued for 10 min before addition of 2.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of aryl sialosides using Mitsunobu conditions

Gao¹,

Schwardt²,

Ernst³

2004

Carbohydrate Research

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Section: Resultsmentioning

confidence: 99%

Synthesis of aryl sialosides using Mitsunobu conditions

Gao¹,

Schwardt²,

Ernst³

2004

Carbohydrate Research

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“…PHARRISO@MCMAIL.CIS.MCMASTER.CA (12). Several syntheses of F-244 and related ana~oguks have been reported (13)(14)(15)(16)(17)(18)(19), and a number of inhibition studies (17)(18)(19)(20)(21) have started to reveal structure-activity correlations. Due to interest in developing F-244 and analogues as antihypercholesterolemic drugs, the structure-activity correlations have focused on comoounds that are similar to F-244 in chemical structure: all have an extended hydrophobic chain at C-4, in most cases terminated with carboxylic acid or carboxymethyl groups, and all but one of the analogues reported to date have a substituent at C-3, usually either hydroxymethyl or alkoxymethyl.…”

Section: Introductionmentioning

confidence: 99%

Irreversible inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A synthase from yeast by F-244 and (RS)-β-butyrolactone

Bell¹,

Saepudin²,

Harrison³

1996

Can. J. Chem.

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The inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) synthase from yeast was compared for both F-244 (1) and (RS)-P-butyrolactone (5). F-244 exhibits irreversible inhibition with an IC,, of 8 nM, similar to that reported for the rat liver enzyme, while the binding constant (IIK,) and inactivation rate constant (kill,,,) are similar to values reported for the human cytoplasmic enzyme. (RS)-P-Butyrolactone (5) also irreversibly inhibits the enzyme, but with much lower efficiency (IC,, 2 mM). The values for K, (9 mM) and kill,,, (0.0078 s-I) for 5 were determined. The results show that kin,,, for 5 and 1 differ by a factor of only 2.5, while KI for 5 is higher by a factor of 1.8 x 10,. Hence, the p-lactone ring is shown to be the sole essential structural feature in 1 for irreversible inactivation of HMG-CoA synthase; however, the remaining functionality enhances the binding of 1 to the enzyme relative to 5.Key words: HMG-CoA synthase, F-244, butyrolactone, irreversible, inhibitor.RCsumC : On a compart l'inhibition de la synthase 3-hydroxy-3-mtthylglutaryl coenzyme A (HMG-CoA) vis-a-vis le compost F-244 (1) anisi que de la (RS)-P-butyrolactone (5). Le composk F-244 prtsente une inhibition irrtversible avec un IC5, de 8 nM, semblable B celle rapportee pour I'enzyn~e du foie de rat, alors que la constante de fixation (IIK,) et la constante de la vitesse d'inactivation (kin,,,) sont toutes les deux semblables aux valeurs rapportkes pour l'enzyme cytoplasmique humain. La(RS)-abutyrolactone (5) inhibe aussi I'enzyme d'une faqon irrtversible, mais son efficacitt est beaucoup plus faible (IC,, de 2 nM). On a dktermink les valeurs de K, (9 mM) et de kin,,, (0,0078 s-I) du composk 5. Les rtsultats montrent que les valeurs de kin,,( des composts 1 et 5 different par un facteur de 2,5 alors que la valeur de K, du compost 5 est 1.8 x lo5 fois plus tlevke que celle du compost 1. On montre donc que le noyau p-lactone est la seule caracttristique structurale essentielle du composk 1 pour I'inactivation irrkversible de la synthase HMG-CoA; toutefois, par comparaison avec le compost 5, les autres fonctions augmentent la fixation du compost 1 B I'enzyme.

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“…10c For the esterification of 12a, a stoichiometric amount of pyridine was required to prevent competing elimination of the alcohol under the reaction conditions. 23 The N-acyl enamide side chain was installed by Cu-catalyzed amidation of 14a,b with amide 15 under the conditions described by Buchwald et al, providing enamides 16a,b in 60-78% yield after re-installation of the acetate group. 24,10f The ring-closing metathesis of 16a,b with Grubbs I catalyst provided the benzolactones 2 and 17 in 31-36% yields after global deprotection.…”

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confidence: 99%