Synchronous bond molecular dynamics of conjugated chlorocyclopropyl alk-yn-enes revealed by ECD and UV-vis.

Chlorocyclopropanes (CCPs) conjugated to alk-yn-enes occur in a unique family of polyketide natural products from marine sponges. Synthesis of several optically enriched analogs of CCPs and measurement of their UV-vis spectra and electronic circular dichroism (ECD) spectra reveal unusually strong hyperconjugation that constrains and aligns the cyclopropyl C-C bond with the π-plane of the distal ene-bond. This alignment imposes a barrier to rotation of at least 5.0 kcal·mol-1 . Comparison of red-shifted Cotton effects in chiral CCPs show the barrier is independent of alkene substituent and establishes an empirical rule for assignment of other CCP-containing natural products.

[1]  T. Molinski,et al.  The Configuration of Distaminolyne A is S: Quantitative Evaluation of Exciton Coupling Circular Dichroism of N, O- Bis-arenoyl-1-amino-2-alkanols. , 2019, Journal of natural products.

[2]  S. Ley,et al.  Convergent total syntheses of callipeltosides A, B, and C. , 2012, Angewandte Chemie.

[3]  G. Mena-Rejón,et al.  The Rotational Barrier in Ethane: A Molecular Orbital Study , 2012, Molecules.

[4]  T. Molinski,et al.  Structure elucidation at the nanomole scale. 3. Phorbasides G-I from Phorbas sp. , 2010, Journal of natural products.

[5]  Tadeusz F Molinski,et al.  NMR of natural products at the 'nanomole-scale'. , 2010, Natural product reports.

[6]  T. Molinski,et al.  A tetrachloro polyketide hexahydro-1H-isoindolone, muironolide A, from the marine sponge Phorbas sp. natural products at the nanomole scale. , 2009, Journal of the American Chemical Society.

[7]  T. Molinski,et al.  Structure elucidation at the nanomole scale. 2. Hemi-phorboxazole A from Phorbas sp. , 2009, Organic letters.

[8]  T. Molinski,et al.  NMR quantitation of natural products at the nanomole scale. , 2009, Journal of natural products.

[9]  Tadeusz F Molinski,et al.  Nanomole-scale natural products discovery. , 2009, Current opinion in drug discovery & development.

[10]  John J. M. Wiener,et al.  Total synthesis and structural revision of callipeltoside C. , 2008, Angewandte Chemie.

[11]  T. Molinski,et al.  Phorbasides A-E, cytotoxic chlorocyclopropane macrolide glycosides from the marine sponge Phorbas sp. CD determination of C-methyl sugar configurations. , 2008, The Journal of organic chemistry.

[12]  T. Molinski,et al.  Ene-yne tetrahydrofurans from the sponge Xestospongia muta. exploiting a weak CD effect for assignment of configuration. , 2007, Organic letters.

[13]  T. Molinski,et al.  Chlorocyclopropane macrolides from the marine sponge Phorbas sp. assignment of the configurations of phorbasides A and B by quantitative CD. , 2007, Journal of the American Chemical Society.

[14]  E. Negishi,et al.  Highly efficient and selective synthesis of conjugated triynes and higher oligoynes of biological and materials chemical interest via palladium-catalyzed alkynyl-alkenyl coupling. , 2006, Organic letters.

[15]  D. Young,et al.  Addition of Cl2C: to (-)-O-menthyl acrylate under sonication-phase-transfer catalysis. Efficient synthesis of (+)- and (-)-(2-chlorocyclopropyl)methanol. , 2005, The Journal of organic chemistry.

[16]  K. Houk,et al.  How large is the conjugative stabilization of diynes? , 2004, Journal of the American Chemical Society.

[17]  O. Meth–Cohn.  Transesterification of Methyl Esters of Aromatic and α,β-Unsaturated Acids with Bulky Alcohols: (−)-Menthyl Cinnamate and (−)-Menthyl Nicotinate , 2003 .

[18]  B. Trost,et al.  Callipeltoside a: total synthesis, assignment of the absolute and relative configuration, and evaluation of synthetic analogues. , 2002, Journal of the American Chemical Society.

[19]  Y. Kishi.  Palytoxin: an inexhaustible source of inspiration—personal perspective , 2002 .

[20]  E. Hu,et al.  Enantioselective total synthesis of callipeltoside A. , 2002, Journal of the American Chemical Society.

[21]  J. Burch,et al.  Asymmetric synthesis of the chlorocyclopropane-containing callipeltoside A side chain. , 2001, Organic letters.

[22]  H. Olivo,et al.  Synthetic studies on the trans-chlorocyclopropane dienyne side chain of callipeltoside A. , 2000, Organic letters.

[23]  A. Alimardanov,et al.  An efficient and stereoselective synthesis of xerulin via Pd-catalyzed cross coupling and lactonization featuring (E)-lodobromoethylene as a novel two-carbon synthon. , 2000, Organic letters.

[24]  Carl R. Johnson,et al.  Sonogashira Coupling of 2-Iodo-2-cycloalkenones: Synthesis of (+)- and (−)-Harveynone and (−)-Tricholomenyn A , 1997 .

[25]  A. Zampella,et al.  Callipeltosides B and C, two novel cytotoxic glycoside macrolides from a marine lithistida sponge Callipelta sp. , 1997 .

[26]  A. Zampella,et al.  Callipeltoside A: A Cytotoxic Aminodeoxy Sugar-Containing Macrolide of a New Type from the Marine Lithistida Sponge Callipelta sp. , 1996 .

[27]  T. Molinski.  Absolute configuration of phorboxazoles A and B from the marine sponge, Phorbas sp. 2. C43 and complete stereochemistry , 1996 .

[28]  T. Molinski,et al.  Absolute Configuration of Phorboxazoles A and B from the Marine Sponge Phorbas sp. 1. Macrolide and Hemiketal Rings , 1996 .

[29]  T. Molinski,et al.  Phorboxazoles A and B: potent cytostatic macrolides from marine sponge Phorbas species , 1995 .

[30]  E. Corey,et al.  A synthetic method for formyl→ethynyl conversion (RCHO→RCCH or RCCR′) , 1972 .