The novel antifungal agents, calbistrins A, B, C and D have been isolated from a strain of Penicillium restrictum (AB 1875C-28). The four congeners were separated by bioactivity directed fractionation using countercurrent chromatography and preparative-HPLC. NMRstudies revealed that the calbistrins each contain a carboxylic acid conjugated tetraene attached through an aliphatic ester linkage to a hexahydronaphthalene system.
39In the course of screening microorganisms for the production of bioactive metabolites, a penicillium was discovered which produced potent activity against Candida albicans. Bioactivity directed fractionation of a fermentation extract provided four new related antifungal agents. The majority of the bioactivity was found in the mycelia, which was filtered off and extracted with acetone. The concentrated extract was partitioned between ethyl acetate and water, CHC13-MeOH-H2Oand methanol-w-heptane. The four calbistrins were recovered as a mixture from the methanol solubles by droplet countercurrent chromatography. They were then separated and further purified by preparative-HPLC using a silica-bonded phenyl column.High resolution FABmass spectrometry in the positive ion mode gave an (M+Na)+ parent mass of 563.2624 for calbistrins A and B, and 565.2774 for C and D; indicating molecular formulae for A and B of C31H40O8and for C and D of C31H42O8.NMRstudies revealed that the calbistrins each contain a carboxylic acid conjugated tetraene which differentiates the isomers A from B, and C form D. In each compoundthis conjugated olefin is attached through an aliphatic ester linkage to a hexahydronaphthalene system. In calbistrins A and B, the hexahydronaphthalene system is fused with a cyclic hemiacetal. In calbistrins C and D this group has been reduced to the open ring diol. Calbistrins A and B exhibit potent activity against Candida albicans and somerelated species. Calbistrins C and Dare less active. The structural characterization of the calbistrins is outlined in this paper. Microbiological and fermentation data are presented in a comparisonpaper.l) Isolation The isolation of the calbistrins was guided by the use of disc diffusion bioassays on agar plates seeded with Candida albicans. Ninety liters of whole beer was filtered through glass wool impregnated paper and the filter cake was dispersed and soaked in sixteen liters of acetone for 16hours (at 4°C). After additional stirring, the mixture was filtered through glass wool impregnated paper and the filter cake was washed with an additional eight liters of acetone. The acetone extract was concentrated on a circulating flash evaporator until approximately four liters of residual aqueous acetone remained. This was extracted with
In the past several years, we have made significant progress in the growth of CdTe buffer layers on Si wafers using molecular beam epitaxy (MBE) as well as the growth of HgCdTe onto this substrate as an alternative to the growth of HgCdTe on bulk CdZnTe wafers. These developments have focused primarily on mid-wavelength infrared (MWIR) HgCdTe and have led to successful demonstrations of high-performance 1024 ϫ 1024 focal plane arrays (FPAs) using Rockwell Scientific's double-layer planar heterostructure (DLPH) architecture. We are currently attempting to extend the HgCdTe-on-Si technology to the long wavelength infrared (LWIR) and very long wavelength infrared (VLWIR) regimes. This is made difficult because the large lattice-parameter mismatch between Si and CdTe/HgCdTe results in a high density of threading dislocations (typically, Ͼ5E6 cm Ϫ2 ), and these dislocations act as conductive pathways for tunneling currents that reduce the R o A and increase the dark current of the diodes. To assess the current state of the LWIR art, we fabricated a set of test diodes from LWIR HgCdTe grown on Si. Silicon wafers with either CdTe or CdSeTe buffer layers were used. Test results at both 78 K and 40 K are presented and discussed in terms of threading dislocation density. Diode characteristics are compared with LWIR HgCdTe grown on bulk CdZnTe.
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