Synthetic studies on stevastelins. 1. Total synthesis of stevastelins B and B3

[Chemical reaction: See text] The synthesis of stevastelin B3 (2) and B (5) are described. In a first approach, epoxy cyclodepsipeptide 8 was considered as a promising candidate for the synthesis of the [15]-membered ring members of the stevastelins; however, the oxirane ring opening, required for the completion of the natural stevastelin synthesis, failed. Thus, we synthesized stevastelin B (5), carrying out the oxirane ring opening earlier in the synthesis and following a synthetic scheme capable of delivering analogues. On the other hand, a translactonization reaction of the [15]-membered ring derivative 59 led to the total synthesis of the natural [13]-membered ring component of the stevastelins family, stevastelin B3 (2).     

Microwave synthesis of zeolites. 2. Effect of vessel size, precursor volume, and irradiation method

The enhancement of synthesis reactions under microwave heating is dependent on many complex factors. We investigated the importance of several reaction engineering parameters relevant to microwave synthesis. Of interest to this investigation were the reaction vessel size, volume of precursor reacted, microwave power delivery, and microwave cavity design. The syntheses of NaY zeolite and beta-zeolite were carried out under a number of varying conditions to determine the influence of these parameters on the nucleation rate, the crystallization rate, and the particle size and morphology. The rates of NaY and beta-zeolite nucleation and crystallization were more rapid in the multimode CEM MARS-5 oven compared to the more uniform field CEM Discover. The faster synthesis rate in the MARS-5 may be the result of the multimode microwave electric field distribution. Slower rates of NaY and beta-zeolite formation observed in the Discover and a circular waveguide may be the result of a more uniform microwave electric field distribution. Changes in reaction vessel size and precursor volume during the microwave synthesis of beta- and NaY zeolite were found to influence the rate of zeolite formation. These results indicate that reactor geometry needs to be considered in the design of systems used for microwave synthesis. Comparative synthesis reactions were carried out with conventional heating, and microwave heating was shown to be up to over an order of magnitude faster for most of these syntheses.     

The total synthesis of (±)-naphthyridinomycin. II. Construction of the pentacyclic carbon skeleton.

A synthesis of an advanced pentacyclic intermediate to the quinone antibiotic naphthyridinomycin (1) is described. The stereoselective synthesis of 2b from tricyclic lactam 3¹ features a regio- and stereoselective, intermolecular amidoalkylation reaction and a Friedel-Crafts ring closure to annelate the aromatic nucleus.     

Metabolites of microorganisms. 130. Synthesis of delta-N-hydroxy-L-arginine

A synthesis of the antibiotically active amino acid, δ-N-hydroxy-L -arginine, starting from L -ornithine is described. In addition a new synthesis of δ-N-hydroxy-L -ornithine, an important building stone of many sideramines, is given.     

Reactivity of 2-halo-2H-azirines. 1. Reactions with nucleophiles.

Nucleophilic substitution reactions of 2-halo-2H-azirines 1a, 1b, 1d, and 1e with potassium phthalimide and aniline allowed the preparation of new substituted 2H-azirines 2-5. The reactions of 2-bromo-2H-azirine 1a with methylamine led to the synthesis of alpha-diimines 7 and 8. 2-Halo-2H-azirines were also established as building blocks for the synthesis of a range of heterocyclic compounds, namely, quinoxalines 10a-10d, 3-oxazoline 14, and 2H-[1,4]oxazines 18 and 20. X-ray crystal structures of alpha-diimine 7, 3-oxazoline 14, and 2H-[1,4]oxazine 18 are reported.     

Synthesis of ent-alantrypinone.

This paper presents a synthesis of ent-alantrypinone (ent-6), the enantiomer of a natural product produced by the fungus Penicillium thymicola. The synthesis revolves around the Li[Me(3)AlSPh]-promoted isomerization of iminobenzoxazine 33 to quinazolinone 34, an N-acyliminium ion cyclization that converts enamide 9 to bridged indole 35, and rearrangement of 35 to oxindole ent-6. Ancillary chemistry that involves thermal fragmentation of an iminobenzoxazine to a nitrile ylide and Me(2)AlSPh-mediated cyclization of oxime ether-ester 22 to pyrrolidinone 23 is also described.     

Regioselective epoxide ring opening. Steroselective synthesis of a tetrahydropyran ring

The stereoselective synthesis of a 2-substituted tetrahydropyran with adjacent alkoxy-bearing stereogenic centre is described. The key steps of this synthesis were the stereoselective epoxidation of an allylic alcohol and the regioselective epoxide ring opening by lithium aluminum hydride. The regio and stereoselective synthesis of a trihydroxyselenide and a trihydroxysulfide is also described. The latter compounds are not suitable for cyclization to tetrahydrofuran ring.     

Preparative solid state chemistry. Recent developments

A survey of recent developments in preparative solid state chemistry shows that, with a knowledge of structural chemistry and reactivity patterns of solids, it is possible to synthesize a variety of new solids possessing novel structures. A distinction is made between synthesis ofnew solids and synthesis of solids bynew methods. Three new routes to solid state synthesis are recognized: the precursor method, and topochemical methods involving redox and ion-exchange reactions. The low-temperature topochemical methods enable synthesis of metastable phases that are inaccessible by the high temperature route. Several illustrative examples of solid state synthesis from the recent literature are presented.     

Diastereotopic selectivity at prochiral carbon centers. A stereodivergent synthesis of the talaromycins.

The transformation of the acyclic precursor previously employed in the synthesis of talaromycin B to the stereoisomeric avian toxin talaromycin A is described. Diastereotopic selectivity at prochiral carbon centers in an acetonide migration and in a subsequent spiroketalization reaction provides the stereocontrol required for the synthesis.     

Polymeric Schiff Bases. VI. The Direct Syntheses of Poly-Schiff Bases

The synthesis of black, high molecular weight polymeric Schiff bases directly from aryldiamines and aryldialdehydes by two methods is described. The first method utilizes benzylideneaniline as the reaction medium. The second method is a direct one-step synthesis involving the reaction of the aryldiamine, aryldialdehyde, aniline, and benzaldehyde. The thermogravimetric analyses of the polymers thus prepared compared favorably with similar polymers prepared by the bis-Schiff base exchange method.     

Bridged to Fused Ring Interchange. Methodology for the Construction of Fused Cycloheptanes and Cyclooctanes. Total Syntheses of Ledol, Ledene, and Compressanolide

The type two intramolecular Diels-Alder reaction (T2IMDA) is an efficient method for the formation of medium rings. The methodology is particularly effective for the construction of seven- and eight-membered rings. A strategy for the synthesis of functionalized cycloheptanes and cyclooctanes has been developed that involves a bridged to fused ring interchange. The T2IMDA provides a synthesis for rigid bridged bicyclic molecules that can be stereoselectively elaborated before ozonolysis of the bridgehead double bond. Following oxidative cleavage, aldol condensation provides fused bicyclic ring systems that otherwise are difficult to synthesize. This methodology is amenable to the synthesis of terpene natural products. This is demonstrated here through total syntheses of (+/-)-ledol and (+/-)-ledene and a formal synthesis of (+/-)-compressanolide.     

Mixed organofluorine-organosilicon chemistry. 13. One-pot synthesis of difluoroaldols from acylsilanes and trifluoromethyltrimethylsilane. application to the synthesis of a difluoro analogue of egomaketone

Difluoroaldol compounds 3 were synthesized in a one-pot procedure involving an acylsilane 1, trifluoromethyltrimethylsilane (TFMTMS), and an aldehyde. The key intermediate of this reaction is a difluoroenoxysilane 2. Ytterbium triflate proved to be a very efficient catalyst for promoting the aldol type reaction under very mild conditions. The potential of this reaction for the convergent synthesis of difluorinated compounds was illustrated by the synthesis of difluoroegomaketone 7d through dehydration of the corresponding aldol compound 3d.     

Convergent solid phase peptide synthesis. II. Synthesis of the 1–6 apamin protected segment on a NBB-resin. Synthesis of apamin

The article deals with the use of the NBB-resin for synthesis of protected segments followed by solid phase segment condenstaion. Solid phse synthesis on a NBB-resin of the segment 1–6 of apamin yielded either the (1–6) apamin-OH segment after photolysis or (1–6) apamin-NH-NH₂ after hydrazinolysis. The two protected segments were purified on Sephaex LH-20 followed by Bio-Beads S-X1 chromatography and respectively coupled onto a resin on which the 7–18 sequence of apamin was assembled stepwise with the standard solid phase procedure. On a portion of the resin, stepwise synthesis was continued to complete apamin. After HF treatment, deprotection of the cysteines, formation of the disulfide bonds and purification, biologically active apamin was obtained in the three cases.     

THE U.V. SENSITIVITY OF BACTERIA: ITS RELATION TO THE DNA REPLICATION CYCLE

Abstract— A striking increase in the shoulder of the u.v. survival curve but no change in the limiting slope is obtained when cultures of Escherichia coli strain TAU complete the DNA replication cycle in the absence of concommitant protein synthesis prior to irradiation. The u.v. sensitivity of protein synthesis or RNA synthesis is not altered significantly by this treatment.
In contrast to the result for strain TAU, there is no significant change in the u.v. survival curve for the u.v. sensitive E. coli B_s-1 when its DNA replication cycle is completed under similar conditions.
Following a period of inhibited protein synthesis there is a delay in the reinitiation of the normal DNA replication cycle when protein synthesis resumes. This delay would allow time for an intracellular repair system to operate before the attempted resumption of normal replication. Strain B_s-1, which is deficient in this repair system, would not be expected to benefit from such a delay, as consistent with the observed results. A model is presented to account for lethality due to attempted DNA replication during a period of repair synthesis. The maximum survival for a given u.v. dose would be predicted for a culture which has completed the normal DNA replication cycle prior to irradiation and which is not permitted to reinitiate the cycle until all possible repair synthesis is completed.     

Gas transport in polyurethane-polystyrene interpenetrating polymer network membranes. I. Effect of synthesis temperature and molecular structure variation

The gas (oxygen and nitrogen) transport characteristics of the interpenetrating polymer network (IPN) membranes of polyurethane/polystyrene were studied. The effect of synthesis temperature, composition, molecular weight of the polyol and aromatic content (of MDI, TDI and HDI) on the gas permeability were analyzed. In the IPN synthesis, first polyurethane was polymerized thermally, and then polystyrene was polymerized by photolytic methods at different temperatures. The permeability coefficient decreased and the separation factor increased with decreasing synthesis temperature due to the miscibility increase. The permeability coefficient showed a minimum value and the separation factor showed a maximum value at ca.25 wt.% polyurethane composition. The permeability coefficient decreased and the separation factor increased with increasing aromatic content in polyurethane component. The morphology and density behavior of the IPN's agreed well with the permeability data. The tensile strength of the membrane increased with decreasing synthesis temperature and with increasing crosslink density and polystyrene content.     

New fluorinating reagents. Part II. Preparation and Synthetic Application of a Saccharin Derived N-Fluorosultam

The synthesis of the new saccharin derived N-fluorosultam 1 is described. A comparative study with commercially available N-fluorosulfonamides shows 1 to be a superior fluorinating reagent for the synthesis of α-fluorocarbonyl compounds.     

Total synthesis of (+)-phorboxazole A exploiting the Petasis-Ferrier rearrangement.

A highly convergent, stereocontrolled total synthesis of the potent antiproliferative agent (+)-phorboxazole A (1) has been achieved. Highlights of the synthesis include: modified Petasis-Ferrier rearrangements for assembly of both the C(11-15) and C(22-26) cis-tetrahydropyran rings; extension of the Julia olefination to the synthesis of enol ethers; the design, synthesis, and application of a novel bifunctional oxazole linchpin; and Stille coupling of a C(28) trimethyl stannane with a C(29) oxazole triflate. The longest linear sequence leading to (+)-phorboxazole A (1) was 27 steps, with an overall yield of 3%.     

Novel non-PEG derived polyethers as solid supports. 2. Solid-phase synthesis studies

Novel non-PEG derived polyether resins, coined SLURPS (Superior Liquid Uptake Resins for Polymer-supported Synthesis), were studied for their performance in solid-phase synthesis. Novel amino functional resins, SLURPS-NH2, were prepared with a loading of up to 8.5 mmol/g and employed successfully in the solid-phase synthesis of Leu-Enkephalin. The peptide was obtained with the same purity when compared to its synthesis with commercial standard poly(dimethyl acrylamide) resins. Furthermore we show loading and cleavage of aromatic carboxylic acids in excellent yield. The advantageous solvent compatibility of our support was demonstrated through the biphasic dihydroxylation of alkenes with OsO4 in t-BuOH/water mixtures producing bound 1,2-diols and synthesis and removal of a bound oxime using ethanol/water mixtures both in excellent yields. Reactions were easily monitored by gel-phase NMR and FTIR. These results show that SLURPS are very well suited for organic transformations using highly polar solvent mixtures and reagents and at much higher loading levels than standard amphiphilic resins of similar solvent compatibility.     

Elaeocarpus Alkaloids. The Synthesis of dl-Elaeokanine-A and dl-Elaeokanine-C.

The synthesis of dl-elaeokanine-A and dl-elaeokanine-C is described by an approach which utilizes a nitrone cyclo-addition to generate a β-aminoketone, which upon annulation produces one or the other of the title alkaloids depending upon conditions.     

Synthesis of heterocyclic analogues of epibatidine via 7-azabicyclo[2.2.1]hept-2-yl radical intermediates. 1. Intermolecular reactions

The synthesis and reactivity of the 7-azabicyclo[2.2.1]hept-2-yl radical has been extensively investigated in inter- and intramolecular reaction processes for the first time. In this work we will present the preparation of the radical and its successful intermolecular reaction with radical acceptors such as tert-butylisocyanide and acrylonitrile. Computational analyses have been carried out to show and explain the mechanisms and stereochemical outcome of these transformations. Overall and from the chemical point of view, a new and convenient synthetic approach has been developed for the synthesis of exo-2-(cyano)alkyl substituted 7-azabicyclo[2.2.1]heptane derivatives, a series of compounds of wide interest for the synthesis of heterocyclic analogues of epibatidine. As a result, we describe here the synthesis of the tetrazoloepibatidines (8 and 15) and the oxadiazoloepibatidine (10).