Toward Creation of a Universal NMR Database for the Stereochemical Assignment of Acyclic Compounds:  The Case of Two Contiguous Propionate Units

Kobayashi, Yohnosuke; Lee, Jinhwa; Tezuka, Kenichi; Kishi, Yoshito

doi:10.1021/ol9903786

Cited by 95 publications

(64 citation statements)

References 6 publications

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“…As we expected, the remote C 5 and C 7 stereocenters would have little effect on the chemical shifts observed in the C 11 -C 16 region of the degradation fragment, it was anticipated that access to a library of diastereomeric C 8 -C 16 subunits would allow a confident configurational analysis. Although Kishi and coworkers (32,33) have elegantly demonstrated the predictive ability of universal NMR databases for stereochemical assignment of acyclic compounds, this did not help the present situation. Our concerns regarding the assignment of C 13 and C 15 directed our initial efforts toward construction of the four C 8 -C 16 diastereomers 27-30 detailed in Scheme 5.…”

Section: Synthesis Of Fragment Library For Nmr Analysismentioning

confidence: 86%

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A

Paterson¹,

Britton²,

Ashton³

et al. 2004

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

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Reidispongiolide A is a representative member of the sphinxolide͞ reidispongiolide group of cytotoxic 26-membered macrolides of marine origin. By interacting with actin in the cell cytoskeleton, the reidispongiolides and sphinxolides are potent microfilament destabilizing agents that represent a promising mechanism of action for developing novel anticancer drugs. An aldol-based synthesis of a library of diastereomers of C 8 -C 16 and C 5 -C 16 fragments and detailed NMR comparison with a reported degradation fragment enabled a configurational assignment for a major part of the reidispongiolide macrocyclic core, thus setting a solid foundation for ongoing synthetic efforts.M arine macrolides provide a fascinating range of structural and functional diversity, which may find application inter alia as specific molecular probes for the investigation of the cytoskeleton and cell cycle events. Unique to eukaryotic cells, the actin cytoskeleton plays a critical role in the determination of cell shape, and in a variety of cellular processes, including cell motility, division, adhesion, and intracellular transportation (1). In comparison with microtubule-interacting agents (2), such as the taxanes and vinca alkaloids, the development of anticancer drugs based on selective binding to actin and disruption of microfilament assembly has attracted relatively little attention. However, recent insight into the role played by microfilaments in cell division and metastasis has highlighted the potential of certain structural classes of actin-binding natural products as useful leads for cancer chemotherapy (3).A growing family of actin-binding macrolides that disrupt microfilament organization includes the scytophycins (e.g., 1, Fig. 1), isolated from the blue-green algae Scytonema pseudohofmanni (4), aplyronines (e.g., 2), isolated from the sea hare Aplysia kurodai (5), and sphinxolides (e.g., 3, planar structure), first reported from an unidentified Pacific nudibranch (6) and later reisolated from the New Caledonian marine sponges Neosiphonia superstes and Reidispongia coreulea, along with the congeneric reidispongiolides (e.g., 4, planar structure) (7,8). A related family of trisoxazole-containing marine macrolides, typified by mycalolide A (5) and jaspisamide A (6), are also antimicrofilament agents (9). Recently, an x-ray crystal structure of the latter compound bound to actin (10) highlighted the importance of the characteristic N-vinyl formamide-containing side chain, common to all these macrolides, in determining their biological activity. Moreover, all these actin-binding macrolides inhibit the proliferation of human cancer cell lines; for example, the scytophycins and sphinxolides exhibit potent cytotoxicity against L1210 and KB cells, with IC 50 values ranging from ng͞ml to pg͞ml (9). In addition, aplyronine A shows potent antitumor activity in vivo and has potential as a clinical candidate (9). Notably, both the scytophycins and sphinxolides circumvent multidrug resistance mediated by the overexpression of P-glycoprotein...

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Section: Synthesis Of Fragment Library For Nmr Analysismentioning

confidence: 86%

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A

Paterson¹,

Britton²,

Ashton³

et al. 2004

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

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“…Another approach for the assignment of relative and absolute configuration of acyclic compounds is based in the Universal NMR Database developed by Kishi's group [38,39]. It is an empirical procedure that relies on the comparison of the observed chemical shifts of compounds with unknown vicinal or proximal centers with libraries of configurationally known stereomodels.…”

Section: Stereochemistrymentioning

confidence: 99%

“…It is an empirical procedure that relies on the comparison of the observed chemical shifts of compounds with unknown vicinal or proximal centers with libraries of configurationally known stereomodels. These 1 H and 13 C NMR databases were first created for the stereochemical assignment of 1,3,5-triols [37,38,40] and then extended for 1,2,3-triols, 1,2,3,4-tetraols, and 1,2,3,4,5-pentaols [41][42][43]. Using this strategy, the relative configuration of 1,3-diol system at C7/C-9 of caylobolide B 12 was assigned as a syn-arrangement since it fits with the carbon chemical shifts of a 1,3-diol model system.…”

Section: Stereochemistrymentioning

confidence: 99%

Nuclear Magnetic Resonance Spectroscopy for Structural Characterization of Bioactive Compounds

Santos

Silva

2014

Comprehensive Analytical Chemistry

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“…Considering the limited availability, as well as the noncrystallinity of mycolactone A/B, we were aware of the difficulties which might be encountered in the assignment of its stereochemistry. Interestingly, we were then engaged in the development of the universal NMR database approach to assign the relative and absolute configuration of unknown compounds without degradation or derivatization (10). We recognized that the universal NMR database approach was uniquely suited to address the stereochemistry of the mycolactone A/B, and began the work.…”

Section: Structurementioning

confidence: 99%

Chemistry of mycolactones, the causative toxins of Buruli ulcer

Kishi

2011

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

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Buruli ulcer is a severe and devastating skin disease caused by Mycobacterium ulcerans infection, yet it is one of the most neglected diseases. The causative toxin, referred to as mycolactone A/B, was isolated and characterized as a polyketide-derived macrolide in 1999. The current status of the mycolactone chemistry is described, highlighting the stereochemistry assignment of mycolactone A/B; total synthesis; the structure determination of mycolactone congeners from the human pathogen M. ulcerans , the frog pathogen Mycobacterium liflandii , and the fish pathogen Mycobacterium marinum ; the structural diversity in the mycolactone class of natural products; the highly sensitive detection/structure-analysis of mycolactones; and some biological activity.

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Toward Creation of a Universal NMR Database for the Stereochemical Assignment of Acyclic Compounds: The Case of Two Contiguous Propionate Units

Cited by 95 publications

References 6 publications

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A

Nuclear Magnetic Resonance Spectroscopy for Structural Characterization of Bioactive Compounds

Chemistry of mycolactones, the causative toxins of Buruli ulcer

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Toward Creation of a Universal NMR Database for the Stereochemical Assignment of Acyclic Compounds: The Case of Two Contiguous Propionate Units

Cited by 95 publications

References 6 publications

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C 5 –C 16 degradation fragment of reidispongiolide A

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C 5 –C 16 degradation fragment of reidispongiolide A

Nuclear Magnetic Resonance Spectroscopy for Structural Characterization of Bioactive Compounds

Chemistry of mycolactones, the causative toxins of Buruli ulcer

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Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C ₅ –C ₁₆ degradation fragment of reidispongiolide A