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.     

Enzymatic Synthesis of Oligopeptide. Part I. Papain-Catalyzed Synthesis of Dipeptide,Tripeptide and Tetrapeptide

Eighteen Z-X-Y-OTNB⁺ type dipeptides, four Z-Val-Cys(Bzl)-X-OTMB tripeptides and a tetrapeptide Z-Val-Cys(Bzl)-Cys(Bzl)-Asn-OTMB have been synthesized by papain-catalyzed reaction in reasonable yield after recystallization. Z-DL-Ala-OH has been resolved through papain-catalyzed synthesis of Z-L-Ala-Leu-OTMB with an optical purity as high as 98.6%. These results show that papain is a good catalyst for oligopeptide synthesis.     

Asymmetric Synthesis of Calyculin C. 1. Synthesis of the C(1)-C(25) Fragment

We report our synthesis of the C(1)-C(25) fragment of serine/threonine phosphatase PP1 and PP2A inhibitor, calyculin C. Synthetic efforts were directed initially toward the synthesis of a spiroketal core fragment (7), which culminated in completion of the bottom half of the natural product. The synthesis of fragment 7 and subsequent elaboration relied on an allylboration strategy for introduction of chirality. The C(1)-C(8) fragment representing the potentially unstable tetraene moiety was introduced as a separate entity.     

Synthesis of Aristotelia-Type Alkaloids. Part VIBiomimetic Synthesis of (+)-Aristofruticosine

(S)-Perilla alcohol ( 5 ) was transformed into (S)-7-(phenylthio)-p-menth-1-en-8-amine ( 11 ) in five steps. Condensation of this building block with 1-(4-methoxyphenylsulfonyl)-1H-indole-3-acetaldehyde ( 12 ) led to the expected imine 15 which cyclized in 54% yield to protected 20-(phenylthio)hobartine 16 upon exposure to anh. HCOOH. Treatment of this intermediate with an alkylating reagent led to (+)-aristofruticosine protected in the indole moiety via an intramolecular, allylic nucleophilic displacement reaction. Subsequent reductive removal of the protecting group completed the first synthesis of the Aristotelia alkaloid (+)-aristofruticosine ((+)- 4 ). This straightforward synthesis confirmed the tentative structure (+)- 4 , proposed by Bick and Hai, and established the hitherto unknown absolute configuration of this metabolite.     

Synthesis of NiGa layered double hydroxides. A combined EXAFS, SAXS, and TEM study. 3. Synthesis at constant pH

The present paper focuses on the direct synthesis of NiGa layered double hydroxides (LDHs) by concomitant addition of Ni and Ga chloride in solution with NaOH solution, at a constant pH value of 6.5. Various Ni/Ga ratios (Ni/Ga = 2, Ni/Ga = 4, or Ni/Ga = 6) were investigated, and samples were collected after successive additions. Each sample was then analyzed by small-angle X-ray scattering (SAXS) to derive information about the shape of the objects formed upon synthesis. In parallel Ni K-edge and Ga K-edge extended X-ray absorption fine structure (EXAFS) analysis were carried out on relevant samples to obtain information on the local structure of the species in suspension. SAXS curves reveal significant changes. At the beginning of the synthesis, for low added volumes (V(s)), the suspension appears to contain both monodimensional and bidimensional objects. For higher V(s), the monodimensional objects disappear and only platelike particles are detected in the suspension. EXAFS results show that all the added gallium atoms are involved in a solid Ni-Ga LDH phase throughout the whole synthesis. In contrast, some nickel cations do not precipitate in the Ni-Ga LDH. At the beginning of the synthesis, for low added volumes they are also involved in the formation of fibrous polycations. For higher added volumes, the fibers are not observed anymore and monomeric nickel species are then present in the suspension.     

Asymmetric Synthesis. XVIII. Stereocontrolled Synthesis of α-Substituted-2-furfurylamines via Chiral Intermediates

The stereocontrolled synthesis of (R)-α-alkyl-2-fur furylamines (5), using (-)-2-hydroxypinan-3-one (1) as a chiral auxiliary, had been studied. The e. e values of (5) were 91.4->98%, which determined by capillary GC (stationary phase: Chirasil-Val).     

Asymmetric Synthesis of Calyculin C. 2. Synthesis of the C(26)-C(37) Fragment and Model Wittig Couplings

We report our synthesis of the C(26)-C(37) fragment of serine/threonine protein phosphatase PP1 and PP2A inhibitor calyculin C (1). Outlined in this paper are synthetic approaches to the two components based on disconnection at the C(33)-N(3) amide bond. We report the successful synthesis of the C(33)-C(37) aza-sugar derived from D-lyxose which was coupled onto a C(26)-C(32) aminooxazole originating from L-pyroglutamic acid. Elaboration of the resulting amide to a fully deprotected C(26)-C(37) fragment of calyculin C completed our synthesis. This provided an appropriate phosphonium salt for use in a Wittig olefination for joining both halves of the natural product.     

2'-C-branched ribonucleosides. 2. Synthesis of 2'-C-beta-trifluoromethyl pyrimidine ribonucleosides

[structure: see text]. The first synthesis of 2'-C-beta-trifluoromethyl pyrimidine ribonucleosides is described. 1,2,3,5-Tetra-O-benzoyl-2-C-beta-trifluoromethyl-alpha-D-ribofuranose (3) is prepared from 1,3,5-tri-O-benzoyl-alpha-D-ribofuranose (1) in three steps and converted to 3,5-di-O-benzoyl-2-C-beta-trifluoromethyl-alpha-D-1-ribofuranosyl bromide (5). The 1-bromo derivative (5) is found to be a powerful reaction intermediate for the synthesis of ribonucleosides. The reaction of silylated pyrimidines with (5) in the presence of HgO/HgBr2 affords exclusively the beta-anomers (6-8). Deprotection of (6-8) with ammonia in methanol yields the 2'-C-beta-trifluoromethyl nucleosides (9-11).     

Sparsomycin analogs. VI. Synthesis and antitumor activity of octylsparsomycin analogs

Five sparsomycin analogs (9-13) were prepared and examined for their ability to inhibit deoxyribonucleic acid (DNA) synthesis in L5178Y lymphoma cells. All of the compounds showed significant activity in the DNA synthesis assay. The compounds having Rc configuration exhibited almost the same activities independently of the configuration at the sulfoxide sulfur atom. Among the Sc isomers, the Rs configuration was advantageous for the appearance of activity.     

5-vinyl pyrimidines. I. Synthesis

A total synthesis of 5-vinyl pyrimidine and some of its substituted derivatives is described. The following vinyl pyrimidines have been prepared: 5-vinyl pyrimidine, 5-vinyl-4,6-dimethoxy pyrimidine, 5-(α-bromo) vinyl-4,6-dimethoxy pyrimidine.     

Synthesis of peptide alkaloids-III. Amino acids and peptides-XXXII. Synthesis of dihydro-zizyphine A and B

Recently we described² a new cyclisation method for the synthesis of ansa peptides by hydrogenolysis of Z-pentafluorophenyl ester and ring closure on the surface of the palladium catalyst. We applied this reaction to the synthesis of the 14-membered ansa peptide dihydro-zizyphine G¹. Here we wish to report the synthesis of the 13-membered ansa peptides dihydro-zizyphine A ($\text{8a}$) and B ($\text{9a}$)³.     

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.     

Synthesis of heparin saccharides IV. Synthesis of disaccharides possessing the structure of a repeating unit of heparin.

The synthesis of disaccharides possessing the structure of a repeating unit of heparin is reported. 2-Acetamido-2-deoxy-4-O-(methyl α-D-glucopyranosyluronate)-D-glucopyranose ( 1 ) and 2-[1-(benzyloxy)formamido]-2-deoxy-4-O-(methyl α-D-glucopyranosyluronate)-D-glucopyranose ( 2 ) have been prepared by two routes, (a) from D-glucose and D-glucosamine, and (b) from D-glucuronolactone and D-glucosamine.     

Synthesis of Azafluorenones using Zeolites.

A convenient method for the synthesis of various azafluorenones (2a-f & 4a-d) by cyclization of substituted arylpyridines (1a-f & 3a-d) using zeolites are described.     

Avermectin-Milbemycin Studies. 3. Synthesis of a Milbemycin-Avermectin Hybrid

An efficient synthesis of a milbemycin-avermectin hybrid ($\text{i.e.}$ 1) has been achieved.     

Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-beta-rotunol and all diastereomers of 6,11-spirovetivadiene

The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has been achieved starting from santonin. The key step is the silicon-guided acid-promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from santonin in several steps involving lactone reductive opening, conjugate addition of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after elimination of the primary hydroxyl group in the side chain, followed by allylic oxidation at C8 and elimination of the tertiary hydroxyl group in the cyclohexane ring. On the other hand, elimination of the hydroxyl group in the side chain and reduction of the hydroxyl in the cyclohexane ring gave (-)-premnaspirodiene and (-)-hinesene. The synthesis of the rest of the diastereomers for these compounds required formal inversion of the C5 spiro carbon. The synthesis of these compounds showed that the structure of (-)-agarospirene isolated from Scapania sp. was erroneously assigned, and it has been corrected to be identical to that of (-)-hinesene.     

Application of Chromium-Arene Complexes in the Organic Synthesis. Efficient Synthesis of Stilbene Phytoalexins

Planar chiral ⁶-arene-Cr(CO)₃ complexes represent highly valuable building blocks for the diastereo- and enantioselective synthesis. Their employment as synthons offer new and unique opportunities for the stereoselective multistep synthesis of complex natural products. The strategy of novel efficient synthesis of stilbene phytoalexins was based on arene chromium chemistry and the chemical and stereochemical effects of the metal unit on the reactivity of complexed arene ligand and stereochemical features of such compounds. Two variants for the construction of the trans-stilbene and diarylethanol framework via facilitated benzylic deprotonation of an ⁶-benzene-Cr(CO)₃ complex and subsequent coupling with para-anisaldehyde in an aldol-type or a Wittig–Horner reaction were suggested.     

Synthesis of polysaccharides. Communication 16. Synthesis of L-arabinopyranans

Summary The synthesis has been effected of 3-0-acetyl-4-0-trityl- and 4-0-acetyl-3-0-trityl-1,2-0-[(l-exo-cyano)ethylidene]-p-L-arabinopyranose by the polycondensation of which (1 4)-L-arabinopyranan and (1 3)-L-arabinopyranan were obtained containing 1,2-trans- and 1,2-cis-glycosidic bonds at a ratio 31.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 1, pp. 196–199, January, 1986.     

Synthesis of (-)-astrogorgiadiol.

Reaction of Rh2(S)-PTPA4 with the (R)-citronellol-derived alpha-diazo-beta-ketoester 1 led to the formation of cyclic beta-ketoester 2 in 95% yield and 48% diastereomeric excess. The purity of 2 was increased to > 99% de after one crystallization. To demonstrate its utility in steroid total synthesis, the beta-ketoester 2 was carried on to secosteroid (-)-astrogorgiadiol (3), a naturally occurring vitamin D analogue with antiproliferative properties.     

Anionic Synthesis of Heteroarm,Star-Branched Polymers. Scope and Limitations

Abstract

The scope and limitations of the following methods for the synthesis of heteroarm star-branched polymers are presented: (a) divinylbenzene linking reactions; (b) coupling reactions with macromolecular silyl halides; and (c) 1,1-diphenylethylene-based living linking reactions. The methodology of using l, 3-bis(1-phenylethenyl)benzene to prepare A₂B₂ hetero 4-armed stars is reviewed, and the synthesis of well-defined (polystyrene)₂(1,4-polybutadiene)₂ heteroarm stars is described. The synthesis of well-defined ABC heteroarm star polymers using macromonomers functionalized with 1, 1-diphenylethylene groups is described.