The synthesis of antifungal antibiotics

Part I describes the successful total synthesis of the antifugal antibiotic kalafungin and a close analogue, 9-deoxykalafungin. The key step, in which all of the carbon atoms present in the target molecules were assembled, is the addition of 2-tert-butoxyfuran to either 2-acetyl-1,4-naphthoquinone or 2-acetyl-8-methoxy-1,4-naphthoquinone. Hydride reduction followed by removal of the tert-butyl protecting group and addition of the C-1 alcohol to the unmasked butenolide afforded intermediate naphthydroquinone dimethyl ethers, which were oxidized to the target molecules with argentic oxide;Part II describes the first successful total synthesis of the trichothec-9-ene skeleton containing oxygenation at both carbon-15 and in the C-ring. The four asymmetric centers present were introduced unambiguously with the correct relative configuration. The synthesis began with a Lewis acid catalyzed Diels-Alder reaction between 1-acetoxy-3-methyl butadiene and 3-hydroxymethyl-3-buten-2-one. The major product from this reaction had the desired stereochemistry at carbons 6 and 11, resulting from cis-endo addition. The thermal reaction afforded the diastereomeric acetoxyketone as the major product. The adduct from the former reaction was transformed to a bicyclic lactone by an intramolecular Knoevenagel condensation. This lactone could be converted into the desired keto-alcohol by reduction of the lactone and nitrile followed by an oxidation and Curtius degradation. Desilylation furnished an alcohol, which was reprotected as the bromoacetate. The third asymmetric center was introduced via an intramolecular alkylation of the regiodefined silyl enol ether of the ketone with the proximate haloester. The (delta)-lactone produced was transformed to an aldehyde, which underwent intramolecular aldolization to introduce the final asymmetric center. Oxidation of the resulting ketol afforded 15-tert-butyldimethyl-silyloxy-13-nortrichothec-9-ene-3,12-dione

A New Resolution: A Review of Resolved

The goal here is to learn healthy disagreement around issues where we haven’t become totally polarized by ideology. Posting about the book Resolved from In All Things - an online journal for critical reflection on faith, culture, art, and every ordinary-yet-graced square inch of God’s creation. https://inallthings.org/a-new-resolution-a-review-of-resolved

Numerical coalescence of chaotic trajectories

Pairs of numerically computed trajectories of a chaotic system may coalesce because of finite arithmetic precision. We analyse an example of this phenomenon, showing that it occurs surprisingly frequently. We argue that our model belongs to a universality class of chaotic systems where this numerical coincidence effect can be described by mapping it to a first-passage process. Our results are applicable to aggregation of small particles in random flows, as well as to numerical investigation of chaotic systems

Educational Software: Why are Teachers Dissatisfied

For adequate computer software teachers and publishers must consult and work together

Synthetic studies toward verrucarol. 2. Synthesis of the AB ring system

A route to the AB ring system of verrucarol is described. The successful scheme involved the formation of the A ring by a boron triacetate catalyzed Diels-Alder reaction. The second ring can be appended by an intramolecular Knoevenagel reaction to afford lactone 12b. This lactone could be converted into the desired keto alcohol 3b by reduction of the lactone and nitrile followed by an oxidation and Curtius degradation

Rearrangements of acyloxyfurans and thiophenes

As part of c1 program for the synthesis of medium-ring compounds, the preparation of the bicyclic ester 1 became necessar

Synthesis of quinone pyrano-.gamma.-lactone antibiotics. 1. Synthesis of 9-deoxykalafungin

An efficient synthesis of 9-deoxykalafungin (lb) in six steps from readily available starting materials is described. The key step, in which all of the carbon atoms present in the target molecule are assembled, is the addition of 2-tert-butoxyfuran to 2-acetyl-l,4-naphthoquinone. Hydride reduction, followed by removal of the tert-butyl protecting group and addition of the C-1 alcohol to the unmasked hutenolide, affords intermediate 13, which can be oxidized with argentic oxide to lb in 17% overall yield

Anesthetic Efficacy of Tricaine Methanesulfonate, Metomidate and Eugenol: Effects on Plasma Cortisol Concentration and Neutrophil Function in Fathead Minnows (Pimephales promelas Rafinesque, 1820)

Anesthetic efficacy, plasma cortisol concentration, and two parameters of neutrophil function (oxidative burst and degranulation of primary granules) were compared among three anesthetics in the fathead minnow: tricaine methanesulfonate (MS 222), metomidate hydrochloride (MTMD), and eugenol (EUG). The optimum anesthetic concentration was determined as: MS 222 75 mg L− 1, EUG 30 mg L− 1 and MTMD 4 mg L− 1. Handling and crowding stress was induced in fish with (SA) and without (S) anesthetic. Plasma cortisol concentration was measured at 0, 30, 90, and 240 min after stress and found to increase at 30 min post-stress in S and SA MS 222 groups, but not in SA MTMD and SA EUG groups. To test the effects of different anesthetics on neutrophil function, fish were divided into a baseline control group, a group exposed to handling and crowding stress (S) and a stressed anesthetized group (SA). Fish were assayed for neutrophil function before and after stress (24 h, 72 h and 7 days). The degranulation of neutrophil primary granules was measured as exocytosis of myeloperoxidase (MPO) using 3, 3′, 5, 5′-tetramethylbenzidine as a substrate. Degranulation of primary granules was decreased to 60–75% of non-stressed control in stressed and fish treated with MS 222, and was not affected when MTMD and EUG were used. The degranulation of primary granules proved to be a useful assay for measuring the effects of stress on neutrophil function in fish. Eugenol and metomidate prevented stress-induced decrease of neutrophil function while MS 222 did not