Syn-SN2' pathway in the reaction of certain .gamma.-(mesyloxy) .alpha.,.beta.-enoates with RCu(CN)MgX.BF3 reagents. Importance of MgX and bulky R group upon the diastereoselectivity

Ibuka, Toshiro; Taga, Tooru; Habashita, Hiromu; Nakai, Kengo; Tamamura, Hirokazu; Fujii, Nobutaka; Chounan, Yukiyasu; Nemoto, Hisao; Yamamoto, Yoshinori

doi:10.1021/jo00057a038

Cited by 53 publications

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“…The synthetic methods reported for ADIs preferentially provide trans ‐amide bond mimics such as ( E )‐ADIs10–14 and ( Z )‐FADIs 15–20. These isosteres have been applied to bioactive peptides and peptidomimetics by employing liquid phase as well as SPPS methodologies 21–26.…”

Section: Introductionmentioning

confidence: 99%

Fmoc‐based solid‐phase synthesis of GPR54‐agonistic pentapeptide derivatives containing alkene‐ and fluoroalkene‐dipeptide isosteres

et al. 2007

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Fmoc‐protected Phe‐Gly‐type (Z)‐alkene dipeptide isostere (ADI) and (E)‐fluoroalkene dipeptide isostere (FADI) were synthesized and applied to Fmoc‐based solid‐phase peptide synthesis (SPPS). These cis‐peptide bond mimetics were introduced into a bioactive pentapeptide [H‐Amb‐Phe‐Gly‐Leu‐Arg‐Trp‐NH2; Amb = 4‐(aminomethyl) benzoic acid], which has potent GPR54 agonistic activity. The resulting pentapeptide derivatives showed low GPR54 agonistic activity, as compared with the parent peptide and (E)‐ADI‐containing derivative. This suggests that the trans‐amide conformer of Phe‐Gly peptide bond of the parent peptide would be significantly important for bioactivity. Contrary to our expectations, a (Z)‐FADI‐containing derivative exhibited essentially no activity, revealing the necessity of critical validation of FADI‐bioisosterism. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 272–278, 2007. This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Section: Introductionmentioning

confidence: 99%

Fmoc‐based solid‐phase synthesis of GPR54‐agonistic pentapeptide derivatives containing alkene‐ and fluoroalkene‐dipeptide isosteres

et al. 2007

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“…Peptide 9 was prepared in five steps from known compound 10. [15,16] From the functional perspective, catalyst 9 affords a result that suggests that the Pro-d-Val amide could well be involved in a catalyst-substrate H-bond in the transition state. As shown in Scheme 4 b, the conversion of 3 to 4 occurs with a much-reduced 16 % ee under catalysis by peptide 9.…”

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Functional Analysis of an Aspartate‐Based Epoxidation Catalyst with Amide‐to‐Alkene Peptidomimetic Catalyst Analogues

2008

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Keywordsepoxidation; peptide; asymmetric catalysis; olefin isostere; fluorine; peptidomimetic The biosynthesis of natural products that contain epoxides represents a powerful stimulus for the study of "epoxidase" enzymes. [i] Likewise, these processes have inspired a generation of science focused on small molecule catalysts that mediate selective epoxidations through a variety of mechanisms. [ii] With respect to the naturally occurring epoxidases, the mechanistic basis of O-atom transfer is often associated with the chemistry of either flavinoid cofactors, P450 enzymes containing a heme group, or chloroperoxidases that lead to stepwise ring formation. [iii] In thinking about the known biosynthetic apparatus for epoxide formation, we became curious about an alternative mode for O-atom transferone based on functional groups available in proteins, but perhaps not well-documented in the biosynthesis of epoxides. In particular, we speculated and recently showed that asparticacid-containing peptides (e.g., 1; Figure 1a) might shuttle between the side-chain carboxylic acid and the corresponding peracid (e.g., 2) creating a catalytic cycle competent for asymmetric epoxidation with turnover of the aspartate-derived catalyst. Such an approach is orthogonal to the Julia-Colonna epoxidation, a complementary peptide-based epoxidation based on a nucleophilic mechanism. [iv] Indeed, as shown in Figure 1b, this new electrophilic epoxidation catalytic cycle mediates the asymmetric epoxidation of substrates like 3 to give products like 4 with up to 92% ee. [v] Mechanistic questions abound in this catalytic system. To date, we have identified a number of relevant aspects. For example, we observed off-catalytic cycle intermediates, including catalytically inactive diacyl peroxides (6). [vi] We also showed that these off-cycle intermediates could be reinserted into the productive pathway through the action of nucleophiles such as DMAP or DMAP-N-oxide (7). On the other hand, the basis of stereochemical information transfer was not immediately clear. Indeed, the high precision delineation of the stereochemical mode of action of chiral catalysts is a critical frontier in the discipline of asymmetric catalysis, whether the catalysts are enzymes or small molecules. With this back-drop, we began a detailed study of the mode of action for catalyst 5.The conversion of 3 to 4 was originally undertaken with the hypothesis that substratecatalyst hydrogen bonding might contribute to transition state organization. [vii] Indeed, a substrate lacking obvious H-bonding capability (phenylcyclohexene) was found to undergo epoxidation with catalyst 5 with low enantioselectivity (~10% ee). Thus, we envisioned several potential loci for contacts between 3 and 5 (Figure 2a). Shown in blue is the site that

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“…Such an explanation might account for the decrease of diastereomeric excess in the obtained a-substituted c-alkoxyallylstannanes when moving from n-Bu [45]. (2) The fact that higher Z selectivities were obtained using magnesium cyanocuprates instead of lithium cyanocuprates might be due to the bidentate character of magnesium (which might interact both with the organocopper moiety and with the syn oxygen of the acetal).…”

Section: Discussionmentioning

confidence: 99%

Preparation of α-substituted γ-alkoxyallylstannanes from β-tributylstannyl acrolein acetals: scope of the method and primary rationalization of the obtained results

Fliegel

Beaudet

Watrelot‐Bourdeau

et al. 2005

Journal of Organometallic Chemistry

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Syn-SN2' pathway in the reaction of certain .gamma.-(mesyloxy) .alpha.,.beta.-enoates with RCu(CN)MgX.BF3 reagents. Importance of MgX and bulky R group upon the diastereoselectivity

Cited by 53 publications

References 0 publications

Fmoc‐based solid‐phase synthesis of GPR54‐agonistic pentapeptide derivatives containing alkene‐ and fluoroalkene‐dipeptide isosteres

Fmoc‐based solid‐phase synthesis of GPR54‐agonistic pentapeptide derivatives containing alkene‐ and fluoroalkene‐dipeptide isosteres

Functional Analysis of an Aspartate‐Based Epoxidation Catalyst with Amide‐to‐Alkene Peptidomimetic Catalyst Analogues

Preparation of α-substituted γ-alkoxyallylstannanes from β-tributylstannyl acrolein acetals: scope of the method and primary rationalization of the obtained results

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