Investigation of Pimelea elongata ("Lakebed Pimelea") afforded 18 tigliane- and daphnane-type diterpenes (1-18). Eight of these were new compounds: four (1-3, 5) tigliane esters and four (7, 8, 10, 11) daphnane orthoesters. The 10 known compounds were 12-O-decanoylphorbol-13-acetate (4), P. simplex subtoxin B (6), wikstroelide E (9), pimelotides A and B (12, 13), gnidiglaucin (14), simplexin (15), huratoxin (16), kirkinine D (17), and 12-β-acetoxyhuratoxin (18). The structures and relative configurations of the new compounds were determined by 1D and 2D NMR spectroscopic studies in combination with MS analyses.

The cytochromes P450 are hemoproteins that catalyze a range of oxidative C-H functionalization reactions, including aliphatic and aromatic hydroxylation. These transformations are important in a range of biological contexts, including biosynthesis and xenobiotic biodegradation. Much work has been carried out on the mechanism of aliphatic hydroxylation, implicating hydrogen atom abstraction, but aromatic hydroxylation is postulated to proceed differently. One mechanism invokes as the key intermediate an arene oxide (and/or its oxepin tautomer). Conclusive isolation of this intermediate has remained elusive and, currently, direct formation of phenols from a Meisenheimer intermediate is believed to be favored. We report here the identification of a P450 [P450cam (CYP101A1) and P450cin (CYP176A1)]-generated arene oxide as a product of in vitro oxidation of tert-butylbenzene. Computations (CBS-QB3) predict that the arene oxide and oxepin have similar stabilities to other arene oxides/oxepins implicated (but not detected) in P450-mediated transformations, suggesting that arene oxides can be unstable terminal products of P450-catalyzed aromatic oxidation that can explain the origin of some observed metabolites.

An efficient route detailing the construction of the central core of pierisformaside C, the first grayanane-type diterpene to possess three central double bonds, is reported.

The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus were deduced to be 4,6,8,10,16,18-hexa- and 4,6,8,10,16-pentamethyldocosanes 2 and 3, respectively. Isomers of 2,4,6,8-tetramethylundecanal 27, 36, and 37, derived from 2,4,6-trimethylphenol, were coupled with the phosphoranes 28 and 29 to furnish alkenes and, by reduction, diastereomers of 2 and 3. Chromatographic and spectroscopic comparisons confirmed 2 as either 6a or 6b and 3 as either 34a or 34b. [structure: see text]

The Caribbean sponges of the genus Plakortis, P. halichondrioides, and P. simplex have provided a series of biologically active furanolactones-the plakortones A-D (1-4) from the former sponge and B-F (2-6) from the latter. The defining motif of the plakortones is a sterically congested 2,6-dioxabicyclo[3.3.0]octan-3-one moiety, the emblematic furanolactone core. This core is efficiently accessed by a palladium(II) mediated hydroxycyclization-carbonylation-lactonization cascade with an appropriate ene-1,3-diol. Total syntheses of plakortones C (3) and F (6) are now described which settle constitutional and stereochemical features in this group of secondary metabolites. Acquisition of plakortone D (4), the most effective activator of SR-Ca(2+)-pumping ATPase, utilized stereodefined lactone cores that resulted from asymmetric dihydroxylation of protected homoallylic alcohol 29. A derived lactone aldehyde was then coupled with an independently generated, sulfone-activated side chain unit, 57. The 11,12-E-double bond, carried through the sequence as a protected, stereodefined diol, was released therefrom by stereospecific syn-elimination via an orthoester derivative. In this way, plakortone D (4) was demonstrated to possess the (3S,4S,6S,10R,11E) configuration. Racemic plakortone E (5) was also acquired by using the Pd(II) induced sequence, but in this case, the required, complete acyclic system 52 was assembled first. Plakortone C (3) resulted from a sequence commencing with (R)-(+)-3-hydroxy-2-methylpropionate, with a derived iodide 76 alkylating the enolate of the butyramide 77 generated from (1S,2S)-(+)-pseudoephedrine. The liberated primary alcohol 79 was converted by standard procedures to key enediol 89 which, with the Pd(II) protocol, afforded the major separable plakortones 90 and 91, with the former being identical with natural plakortone C (3). Very mild hydrogenation of 90 afforded a saturated plakortone, identical with natural plakortone F (6), thus establishing its structure and absolute stereochemistry. Available information on the stereoselective routes to plakortones E (5) and B (2) are also outlined, so that the constitution and absolute stereochemistry of plakortones B-F are now established.

Common oxidants used in chemical synthesis, including newly developed perruthenates, were evaluated in the context of understanding (and better appreciating) the sensitiveness and associated potential hazards of these reagents. Analysis using sealed cell differential scanning calorimetry (scDSC) facilitated Yoshida correlations, which were compared to impact sensitiveness and electrostatic discharge experiments (ESD), that enabled sensitiveness ranking. Methyltriphenylphoshonium perruthenate (MTP3, 8), isoamyltriphenylphosphonium perruthenate (ATP3, 7) and tetraphenylphosphonium perruthenate (TP3, 9) were found to be the most sensitive followed by 2‐iodoxybenzoic acid (IBX, 2) and benzoyl peroxide (BPO, 10), whereas the most benign were observed to be Oxone (12), manganese dioxide (MnO2, 13), and N‐bromosuccinimide (NBS, 17).

No abstract

The major cuticular hydrocarbons from the cane beetle species Antitrogus parvulus are 4,6,8,10,16-penta- and 4,6,8,10,16,18-hexamethyldocosanes, 1 and 2, respectively. Stereoisomers of 2,4,6,8-tetramethylundecanal of established relative stereochemistry were derived from 2,4,6-trimethylphenol and were then coupled with appropriate methyl-substituted phosphoranes 62 and 25 to furnish alkenes, which on reduction provided diastereomers of 1 and 2, respectively. Capillary gas chromatography, mass spectrometry, and high resolution 13C NMR spectroscopy confirmed 1 as either 84a or 84b and 2 as either 15a or 15b. The novelty of these structures and their relative stereochemistry is briefly related to polyketide assembly.