Synthesis of novel proline-thiazole based cyclic hexa- and octapeptides

Novel proline-thiazole based cyclopeptides were produced by cyclooligomerisation of an L-proline thiazole amino acid HCl in the presence of pentafluorophenyl diphenylphosphinate (FDPP) or diphenyl phosphorazidate (DPPA).     

Synthetic studies towards congeners of phomactin A. Re-examination of the structure of Sch 49028

The total syntheses of the epoxy cyclic hemiacetal structures 8 and 9, which are isomeric with the structure 6 proposed for the phomactin known as Sch 49028 isolated from the marine fungus Phoma sp. are described. Neither of these structures showed spectroscopic data consistent with those reported for the purported natural product, adding credibility to the proposal that the structure Sch 49028 does not exist in nature and that its NMR spectroscopic data should have been assigned as phomactin A (1).     

Cobalt π-cations in carbocyclic ring constructions

In a combination of cobalt-mediated cationic and free radical chemistry, treatment of the allyl silane substituted β-hydroxycobaloxime 13 with pTSA led predominantly to the trans-disubstituted cyclopentane 14, which on irradiation with TEMPO produced 15. In a similar manner, the cobaloxime 18 was cyclised to 19 in the presence of pTSA which, on irradiation with a sunlamp then underwent radical mediated cyclisation to the substituted indane 20.     

A total synthesis of phomactin A

A total synthesis of phomactin A (1) based on a Cr(II)/Ni(II) macrocyclisation from the aldehyde vinyl iodide 11, leading to 12, followed by elaboration of the epoxyketone 16, which then undergoes spontaneous pyran-hemiacetal formation on deprotection, is described.     

Marine Metabolites and Metal Ion Chelation: The Facts and the Fantasies

The marine environment is a seemingly inexhaustible treasury of organisms whose secondary metabolites bear witness to the lavishness and inventiveness with which nature is able to manipulate molecular architecture. But to what purpose are these diverse and often grotesque compounds produced? This review is founded on the premise that some of them may be involved in the uptake and transport of metal ions present in the aquatic milieu. Many metabolites produced by terrestrial organisms are known to act as ionophores, but the case for similar behavior by their marine counterparts is far hazier. Notwithstanding the relative abundance of certain metal ions in the oceans, and of metabolite structures possessing features that should facilitate the chelation of metal ions, few attempts to establish a connection between these two phenomena have been reported. We have whittled down the voluminous literature of natural products derived from marine sources to expose a core of observations and speculations germane to our premise. These facts and fantasies are evaluated in this review. A mere handful of metal-containing complexes has actually been isolated; furthermore, attempts to prepare such complexes in vitro are rare, and spectroscopic evidence for metal–metabolite interactions, whether in vivo or in vitro, is not common. Only with the vanadium-sequestering tunichromes does a logical (but by no means complete) picture begin to emerge. In several other cases, the plausibility of metal chelation, though mooted by authors, remains unsupported by experimental evidence. However, continuing efforts to obtain structural, and particularly conformational, information on the metabolites by means of X-ray crystallography, nuclear magnetic resonance spectroscopy, and molecular mechanics calculations would seem to provide the key to a rational approach to this neglected topic. On the basis of recent studies dealing with such structural aspects, we present a selection of candidate compounds, some of which are the targets of our own synthetic attentions, whose potential for binding to metal cations merits further research.     

Ab initio calculations on peptide-derived oxazoles and thiazoles: Improved molecular mechanics parameters for the AMBER* force field

Ab initio calculations at the RHF/6-31G* and MP2/6- 31G*//RHF/6-31G* levels of theory are performed for 2-methyl-4-carboxamido-oxazoles and -thiazoles, including rotational profiles for the ring-carboxamide bond, which showed the expected conjugation and hydrogen bonding effects. On the basis of these data, newly optimised stretch, bend and torsional parameters for the AMBER* force field are derived, along with CHELPG-fitted partial atomic charges.     

The mass spectra of the pyrethrins and related compounds

The mass spectra of the natural pyrethrins, allethrin, the chrysanthemic acid, and the rethrolonyl and rethronyl portions of the insecticidal esters are presented, and their main fragmentation pathways are discussed.     

A total synthesis of (+/-)-phomactin A

A total synthesis of the PAF antagonist phomactin A (1), isolated from the marine fungus Phoma sp. is described. The synthesis is based on a Cr(II)/Ni(II) macrocyclisation from the aldehyde vinyl iodide 14, leading to the key phomactatrienol intermediate 16a, followed by elaboration of 16a to the epoxyketone 21, which undergoes spontaneous pyran and hemiacetal ring formation to 1 on deprotection with DDQ.