Showing papers on "Total synthesis published in 1976"

Studies Directed toward the Synthesis of Prostaglandins. Useful Boron-Mediated Olefin Syntheses

Abstract: The reactions of bis(2-ethylcyclopentyl)borane, dicyclopentylborane, with 3- (tert -butydimethylsiloxy)-1-octyne and subsequent iodine-promoted rearrangement to 2 olefins or unsymmetrical acetylenes are reported. Mixed dialkylboranes are also examined in this olefin-acetylene cross process. Significant amounts of thexyl-migrated acetylenic by-products are observed in several instances. The synthesis of either E- or 2-1,2-disubstituted olefins by roaction of boronic esters with both (E)- and (2)-alkenyllithium reagents is examined. This study demonstrates that 50-70% yields of either E- or 2-1,2-disubstituted olefins are obtainable from the aforementioned reagents. The overall objectives in this investigation are to assess the potential of employing organoborane intermediates in the coupling of the C13-C20 prostaglandin olefinic side chain to cyclopentenoid precursors. As part of our program directed toward the total synthesis of prostaglandin hormones we recently reported a general stereospecific approach to the synthesis of cis-2-alkyl-2-cyclopentene-1,4-diols (1) via the three-step sequence illustrated below.2 This expeditious synthetic scheme readily affords a 0

Syntheses of (2R, 4′R, 8′R)‐α‐Tocopherol and (2R, 3′E, 7′E)‐α‐Tocotrienol

Abstract: Reaction of trimethyl-hydroquinone with methyl vinyl ketone in acidic methanol gave rac.-2-methoxy-2,5,7,8-tetramethyl-chroman-6-ol (8). This acetal was converted in four steps to rac.-(6-hydroxy-2,5,7,8-tetramethyl-chroman-2-yl)acetic acid (13). Acid 13 was readily resolved with α-methyl-benzylamine to give the (S)-enantiomer 14. Treatment of the unwanted (2 R)-isomer with acid regenerated 13, thus leading to an efficient use of this compound. Employing a side chain derived from phytol, 14 was converted to (2R, 4′R, 8′R)-α-tocopherol (1d, ‘natural’ vitamin E). A reaction sequence from 14 involving two highly stereoselective Claisen rearrangements has provided the first total synthesis of (2R,'E,7′E)-α-tocotrienol (2d).

Asymmetric induction in 19-norsteroid total synthesis.

Abstract: Asymmetric induction in 19-norsteroid total synthesis is discussed. It should be noted that the (S)-(+)-enedione can be made available by cyclization of the triketone with (S)-proline and its derivatives (asymmetric synthesis). Also mention must be made of the elegant approaches to progesterone and 11-substituted progesterones using biomimetic polyolefin cyclizations in which substantial asymmetric induction at several chiral centers is observed (diastereoselective synthesis). It is concluded that the successful utilization of asymmetric transformations demonstrated in the steroid field defines the potential of such processes and bodes well for their equally successful application in other areas of natural product synthesis.

Synthetic Studies on Lycoricidine and Related Compounds. II. Total Synthesis of (±)-Lycoricidine

Abstract: The first total synthesis of (±)-lycoricidine and confirmation of its full structure were established. In the synthesis of a key compound, 4H-r, 1H-trans, 2H-cis, 10bH-trans, -1-(2'-tetrahydropyranyloxy)-2-hydroxy-8, 9-methylenedioxy-1, 2, 4a, 10b-tetrahydro-6 (5H)-phenanthridone (14), Sharpless's procedure for preparation of allyl alcohols from epoxides using selenophenolate and hydrogene peroxide was applied.

Total synthesis of (.+-.)-cedrol and (.+-.)-cedrene via an intramolecular Diels-Alder reaction

Abstract: A total synthesis of racemic cedrol and cedrene is described in which a key step is the intramolecular Diels–Alder reaction of alkyl cyclopentadiene 3 to give the tricyclic olefin 4. Oxidation of t...

Synthese von Humaninsulin. II. Aufbau des cyclischen Fragments A(1–13)†‡

Abstract: Synthesis of human insulin. II. Preparation of the A(1–13) fragment. The present report gives a detailed account of the synthesis of the protected tridecapeptide A(1–13), BocGlyIleValGlu(OBut)Gln Ser(But)LeuOH (20), an essential intermediate in the recently published total synthesis of human insulin [1]. The main feature in the synthesis of 20 was the specific formation of a disulfide bond between A6 and A11 in the presence of an additional cysteine residue (A7). The selective ring closure was accomplished with the segment A(6–13), HCys(Trt)Cys(Acm)Thr(But)Ser(But)IleCys(Trt)Ser(But)LeuOH (18), which was obtained by way of conventional synthesis routes. Treatment of 18 with iodine in trifluoroethanol formed the desired disulfide bridge from the two S-trityl-cysteine residues without affecting the S-acetamidomethyl-protected cysteine A7. A final azide coupling with the N-terminal derivative A(1–5) (3) provided the tridecapeptide fragment 20 as a crystalline compound.

Total synthesis of the macrocyclic antibiotic (+/-)-pyrenophorin.

Abstract: The total synthesis of the macrocyclic antibiotic pyrenophorin (8,16-dimethyl-1,9-dioxacyclohexadeca-3,11-diene-2,5,10,13-tetraone)(16) is described, involving the use of the 2-(p-tolylsulphonyl)ethyl ester as a selectively removable protecting group for the carboxy-function, and di-imidazol-1-yl ketone as a lactonising reagent.

Reaktionen an Indolderivaten, XXX Die stereoselektive und stereospezifische Totalsynthese der Geissoschizin‐Isomeren

Abstract: Uber eine stereoselektive und stereospezifische Claisen-Umlagerung kann die exocyclische, Z-konfigurierte Doppelbindung des 19,20-Isogeissoschizins (4a) eingefuhrt werden. Die Konfiguration der Produkte lies sich durch Korrelation mit Naturstoffen beweisen. Reactions with Indole Derivatives, XXXThe Stereoselective and Stereospecific Total Synthesis of Geissoschizine Isomers The exocyclic, Z-configurated double bond of 19,20-isogeissoschizine (4a) can be introduced via a stereoselective and stereospecific Claisen rearrangement. The configuration of the products is proven by correlation to natural products.

A total synthesis of myrrhine, (±)-hippodamine, and (±)-convergine

Abstract: A seven-step, stereoselective, total synthesis of the ladybug defensive substance myrrhine (5) from 2,4,6-collidine is presented. Successive alkylation and acylation of 2,4,6-collidine followed by ketalization provides 2-(3-[2-(1,3-dioxolanyl)]propyl)-6-(2-methyl-2-[1,3-dioxolanyl]methyl)-4-methylpyridine (14). Sodium–alcohol reduction gives the corresponding all-cis piperidine 17. Hydrolysis of 17 followed by acid-catalyzed cyclization provides ketone 26. Reduction of the carbonyl group in 26 gives myrrhine (5). Cyclization using pyrrolidine – acetic acid gives a mixture of ketones (26 and 31). Reduction of 31 gives (±)-hippodamine (4). Oxidation of (±)-hippodamine with peracid gives (±)-convergine (3).

A Stereospecific Synthesis of Biotin from an Aromatic Precursor. Preliminary Communication

Abstract: The total synthesis of the important natural product biotin 1 from the readily available keto diester 3 is described. This approach features the stereospecific hydrogenation of the thiophene intermediate 19 as the key synthetic step. The required differentiation of the diacid functionality of compound 7 is achieved by selective lactam formation with the terminal acid to yield the 8-membered lactam 8. A modified Curtius reaction then affords the rearranged diurethane 18 through a series of acyl transfers. Finally, a novel conversion of the 3, 4-diurethane moiety to the imidazolidone portion of biotin is utilized to complete the synthesis.

Die Synthese von 2,2′-Dinor-carotinoiden

Abstract: The Synthesis of 2,2′-Dinor-carotenoids. 2,2′-Dinor-carotenoids which include the naturally occurring actinioerythrol (1) and the blue carotenoid violerythrin (2) have been obtained by total synthesis. The synthesis starts with acetone and acetylene and yields compounds 1 and 2 as well as other carotenoids of the same type.