Branched triangulanes: general strategy of synthesis

Zefirov, N. S.; Kozhushkov, Sergei I.; Уграк, Б. И.; Lukin, K. A.; Kokoreva, O. V.; Yufit, D. S.; Struchkov, Y. T.; ZOELLNER, S.; Boese, Roland; Meijere, Armin de

doi:10.1021/jo00028a054

Cited by 33 publications

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“…However, it should be noticed that the CP ring and the C(2)--C(3) double bond in (1) are parts of the strained, rigid bicyclic system and the spiro conjugation of CP with another small ring is known to result in significant elongation of the distal bond, which decreases the strain at the spiro atom. This effect was discussed by Boese (Boese, Miebach & De Meijere, 1991) on comparing the spiropentane and [n]rotane structures and was also observed in our previous studies of triangulane structures (Yufit, Lukin, Kozhushkov, Struchkov & Zefirov, 1991;Zefirov, Kozhushkov, Ugrak, Lukin, Kokoreva, Yufit, Struchkov, Zoellner, Boese & De Meijere, 1992 The small lengthening of the C(2)--C(5) bond is probably also caused by the strain in the bicyclic system. The lengths of the double bonds in the vinyl substituted CP ring are not sensitive to conjugation (Allen, 1981), and therefore the absence of any elongation of the C(2)=C(3) bond distance in (1) is not unusual.…”

Section: Methodssupporting

confidence: 72%

Structure of 1,2-bis(spiro[2.3]hex-4-ene-4-yl)ethane

Yufit¹,

Struchkov²,

Lukin³

et al. 1993

Acta Crystallogr C

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Section: Methodssupporting

confidence: 72%

Structure of 1,2-bis(spiro[2.3]hex-4-ene-4-yl)ethane

Yufit¹,

Struchkov²,

Lukin³

et al. 1993

Acta Crystallogr C

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“…The resulting product 11 was subjected to base-induced elimination, deprotection, and oxidation in sequence to give 13 . Conversion of 13 to SPA ( 15 ) was achieved by the treatment with diazomethane and lead tetraacetate to give 14 , followed by alkaline hydrolysis of the methyl ester (Scheme ) 5g, in aqueous THF solution (pH 8−8.5) afforded the desired spiropentylacetyl-CoA ( 16 ).…”

Section: Resultsmentioning

confidence: 99%

“…Conversion of 13 to SPA (15) was achieved by the treatment with diazomethane and lead tetraacetate to give 14, followed by alkaline hydrolysis of the methyl ester (Scheme 2). 14 Condensation of SPA with isobutyl chloroformate and coupling to coenzyme A 5g,15 in aqueous THF solution (pH 8-8.5) afforded the desired spiropentylacetyl-CoA (16). This compound was later purified by a HPLC Partisil-C 18 column, and the overall yield from MCPA (13) 16) on the catalytic activity of MCAD was investigated by the incubation of MCAD with 10 mol equiv of SPA-CoA under aerobic conditions at 25 °C.…”

Section: Resultsmentioning

confidence: 99%

“…[r-3 H]Spiropentylacetyl-CoA (18). By adapting a similar procedure used for the synthesis of spiropentylacetic acid (15) from methyl spiropentylacetate (14), the labeled analogue was obtained from methyl [R-3 H]spiropentylacetate (17) in 76% (0.13 g). The [R-3 H]spiropentylacetic acid was later coupled with coenzyme A to give the title compound in 72% yield (41 mg), with a specific activity of 0.32 mCi/ mmol.…”

Section: -[2-(1-chloro-1-methylcycloprop-2-yl)ethoxy]tetrahydropyran ...mentioning

confidence: 99%

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Spiropentylacetyl-CoA, A Mechanism-Based Inactivator of Acyl-CoA Dehydrogenases

Zhou

Dakoji

et al. 1998

J. Am. Chem. Soc.

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Acyl-CoA dehydrogenases (ACDs) are FAD-dependent enzymes that catalyze the conversion of an appropriate fatty acyl-CoA thioester substrate to the corresponding trans-α,β-enoyl-CoA product. Early studies have shown that the dehydrogenation is stereospecific and is initiated by the abstraction of the pro-R α-H, followed by the transfer of the pro-R β-H, as a hydride equivalent, to the bound FAD. However, recent studies of the inactivation of ACDs by a metabolite of hypoglycin A, (methylenecyclopropyl)acetyl-CoA (MCPA-CoA), led to an alternative mechanism in which the reducing equivalent is delivered from the initially formed α-anion to the bound FAD via a single electron transfer process. To further explore the observed mechanistic discrepancy, we have reexamined the inhibitory properties of a closely related MCPA-CoA analogue, spiropentylacetyl-CoA (SPA-CoA), which was previously reported as a tight-binding inhibitor for ACDs. In contrast to early results, our data showed that SPA-CoA is a mechanism-based inhibitor for pig kidney medium-chain acyl-CoA dehydrogenase (MCAD) and Megasphaera elsdenii short-chain acyl-CoA dehydrogenase (SCAD) and that the inactivation is time-dependent, active-site-directed, and irreversible. More importantly, both (R)- and (S)-SPA-CoA could effectively inactivate MCAD, and the resulting inhibitor−FAD adducts appear to have one of the three-membered rings of the spiropentyl moiety cleaved. Since the inactivation is nonstereospecific with respect to Cβ−C bond scission, the ring opening of SPA-CoA leading to enzyme inactivation is likely initiated by a spiropentylcarbinyl radical. Such a radical-induced ring fragmentation is expected to be extremely facile and may bypass the chiral discrimination normally imposed by the enzyme. Thus, these results are consistent with our early notion that MCAD is capable of mediating one-electron redox chemistry. Interestingly, it was also found that (R)-SPA-CoA is an irreversible inhibitor for SCAD, while the S-epimer is only a competitive inhibitor for the same enzyme. The selective inhibition exhibited by these compounds against two closely related dehydrogenases is likely a consequence of the distinct steric and electronic demands imposed by the active sites of MCAD and SCAD. Such information is important for the design of novel class-selective inhibitors to control and/or regulate fatty acid metabolism.

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“…The spiro-annelation of cyclopropanes leads to the family of [ n ]triangulanes, − whose infinite extension would provide hitherto unknown polytriangulane , which is a hydrocarbon with the formula C n H n . In constructing triangulanes beyond [3]triangulane, , linear, helical, and branched isomers ensue (Scheme ).…”

Section: Introductionmentioning

confidence: 99%