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The 2S configuration of the marine natural product distaminolyne A was recently disputed based upon total synthesis, yet paradoxically supported by a second independent total synthesis from a different research group. We now verify the 2S configuration of distaminolyne A by extensive chiroptical studies and support the veracity of the EC ECD method originally used to prove it. The origin of the apparent paradox appears to lie in the limits of precision of polarimetry in the context of weakly rotatory molecules, which strikes a cautionary note on the reliability of “reassignment” of natural product configurations based solely on specific rotation.

In our search for new antibiotic adjuvants as a novel strategy to deal with the emergence of multi-drug resistant (MDR) bacteria, a series of succinylprimaquine-polyamine (SPQ-PA) conjugates and derivatives of a cationic amphiphilic nature have been prepared. Evaluation of these primaquine conjugates for intrinsic antimicrobial properties and the ability to restore the antibiotic activity of doxycycline identified two derivatives, SPQ-PA3-8-3 and SPQ-PA3-10-3 that exhibited moderately strong intrinsic activity against the Gram-positive bacteria Staphylococcus aureus and the yeast Cryptococcus neoformans. None of the analogues were active against the Gram-negative bacterium Pseudomonas aeruginosa. However, in the presence of a sub-therapeutic amount of doxycycline (4.5 µM), both SPQ-PA3-4-3 and the SPQ-PA3-10-3 displayed potent antibiotic adjuvant properties against P. aeruginosa, with MIC's of 6.25 µM. A series of derivatives were prepared to investigate the structure-activity relationship that explored the influence of both a simplified aryl lipophilic substituent and variation of the length of the polyamine scaffold on observed intrinsic antimicrobial properties and the ability to potentiate the action of doxycycline against P. aeruginosa.

An acetylenic 2-amino-3-alcohol, distaminolyne B (2), isolated from the New Zealand ascidian Pseudodistoma cereum, is reported. The isolation and structure elucidation of 2 and assignment of 2S,3S absolute configuration (AC) using the exciton coupled circular dichroism technique are described. Using a methodologically facile workflow, the same AC was also established by analysis of specific rotation, terminal methyl C-1 δ C chemical shift, and NH δ H and J values of the N,O-diacetate derivative.

Alkaloids Alkaloids U 0600Distomadines A and B, Novel 6-Hydroxyquinoline Alkaloids from the New Zealand Ascidian, Pseudodistoma aureum. -Distomadines A and B, (I), tetracyclic guanidine-containing hydroxyquinoline alkaloids, are isolated from the plant and characterized by spectroscopic methods and chemical derivatization. Distomadine A (Ia) is obtained as an optically active, fluorescent yellow powder while distomadine B (Ib) is obtained as a 1:2 mixture of (Ib) and 2'-deoxyadenosine. Distomadine A displays mild antifungal activity but is inactive in a range of antitumor, antiviral, anti-inflammatory and antimycobacterial assays. In addition, three known methyl esters of fatty acids are also identified. Eicosapentaenoic acid methyl ester shows mild cytotoxicity to a non-malignant cell line. -(PEARCE, A. N.; APPLETON, D. R.; BABCOCK, R. C.; COPP*, B. R.; Tetrahedron Lett. 44 (2003) 20, 3897-3899; Dep. Chem., Univ. Auckland, Auckland, N. Z.; Eng.) -H. Hoennerscheid 33-203