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1.
A 5-exo-dig radical cyclisation of the bromoamide 34 derived from the enantiopure α-ethynyl substituted amino alcohol 31 led to a 2:1 mixture of β-C3 and α-C3 methyl epimers of the pyrrolidinone 35a-36a in a combined yield of 73%. Treatment of the homoallylic alcohol 35b, derived from 35a, with OsO4-TMEDA, gave a single diastereoisomer of the pyrrolidinone triol 37, resulting from selective dihydroxylation from the β-face, i.e. syn to the CH2OH group of 35b. The pyrrolidinone triol 37 is a potential common precursor, cf. 9, to the spiro β-lactone pyrrolidinone 8 and the γ-lactone pyrrolidinone 10 ring systems in oxazolomycin A (1) and neooxazolomycin 2, respectively. Sequential protection of the 1,2-diol functionality in 37 as the acetonide 39, and the primary alcohol group in 39 as the SEM ether 41a, followed by methylation of the nitrogen centre in 41a, using NaH-MeI, then gave the selectively protected pyrrolidinone 42. 相似文献
2.
A highly stereoselective synthesis of the C(22)-C(36) fragment 2 of reidispongiolide A is described. This synthesis features the highly stereoselective mismatched double asymmetric crotylboration reaction of the aldehyde derived from 5 and the new chiral reagent (S)-(E)-7 that provides 12 with >15:1 dr. Subsequent coupling of the derived vinyl iodide 3 with aldehyde 16 provided allylic alcohol 17, that was elaborated by three steps into the targeted reidispongiolide fragment 2. 相似文献
3.
Christopher A BurnettJason Lagona Anxin WuJennifer A Shaw Daniel CoadyJames C Fettinger Anthony I DayLyle Isaacs 《Tetrahedron》2003,59(11):1961-1970
Glycoluril derivatives bearing free ureidyl groups (1) and bis(cyclic ethers) (2) are the fundamental building blocks for the synthesis of cucurbituril, its derivatives, and its congeners. The known derivatives of 1 and 2 fall into two main classes—those bearing alkyl or aryl functional groups on their convex face. In this paper we present a third class of glycolurils, namely those bearing substituents that are electron withdrawing in character. This class of compounds carries carboxylic acid derived functional groups on their convex face and are derived from diesters 1e and 2e. An improved synthesis of 1e and 2e is reported and their modification described. For example, 1e and 2e are converted into secondary amides (10-15) by heating in solutions of the neat primary amines. The secondary amides can be transformed into imides (19-22, 24, 25) by heating with PTSA in ClCH2CH2Cl. The isolation of these compounds in pure form in high yields is accomplished by simple and scalable washing or recrystallization procedures. We also present the X-ray crystallographic characterization of bis(cyclic ethers) 2e, 8, and 22. We anticipate that the ready availability of ester, carboxylate, acid, secondary amide, imide, and tertiary amide derivatives of 1 and 2 will expand the scope of the synthesis of cucurbituril derivatives by providing a new class of building blocks with electron withdrawing substituents. 相似文献
4.
Synthesis of methylene-2-ethynylcyclopropane analogues of nucleosides 12a, 12b, 13a, and 13b is described. Ethyl methylenecyclopropane carboxylate 14 was hydroxymethylated to give alcohol 15, which was reduced to diol 16. Selective protection with tert-butyldimethylsilyl group gave derivative 17, which was oxidized to aldehyde 18. Wittig reaction with CBr4 gave dibromoalkene 19. Elimination of both bromine atoms afforded methylene-2-ethynylcyclopropane 20. Bromoselenenylation using N-bromosuccinimide and diphenyldiselenide gave intermediate 21. Alkylation of adenine and 2-amino-6-chloropurine with 21 provided the Z,E-isomeric mixtures 22a and 22c. Oxidation afforded selenoxides 23a and 23c. Mild thermolysis furnished methylenecyclopropanes Z-24a, E-24a, and 24c. Deprotection and separation of Z,E-isomers gave adenine analogues 12a and 13a, and 2-amino-6-chloropurine intermediates 12c and 13c. Hydrolytic dechlorination of 12c and 13c afforded guanine analogues 12b and 13b. Adenine Z-isomer 12a inhibits replication of Epstein-Barr virus through its cytotoxicity. The E-isomer 13a is a substrate for adenosine deaminase. 相似文献
5.
The reaction of [60]fullerene with organolithium and Grignard reagents carrying orthoester, acetal or other end groups yielded adducts 3-5 at the 6-6 bond of C60 after quenching with trifluoroacetic acid. The adducts could be easily methylated or benzylated with methyl iodide or benzyl bromide in the presence of potassium tert-butoxide to yield exclusively the 1,4-disubstituted C60 6 and 7a,b. Cleavage of the orthoester, acetal and silylether groups gave the corresponding carboxylic acid 9, aldehydes 10a,b and 11 and alcohols 12 and 13a,b. The carboxylic acid 9 readily reacted with alanine ethyl ester under standard peptide coupling conditions to give 14 in 55% yield. Attempts to generate a silyl enol ether from the reaction of aldehyde 10b with TIPSOTf and triethylamine failed. Instead the reaction led to a cyclized ether 16a (or alcohol 16b in the absence of silylating agent) resulting from the addition of an initially formed fulleride anion to the aldehyde group. The corresponding acetal 4b reacted similarly. The reaction of aldehyde 10b with aniline also gave a cyclized product 19. Surprisingly, aldehyde 11, which no longer carried an acidic fullerene proton reacted with aniline to give a product 20 resulting from an intramolecular Diels-Alder reaction followed by aromatization of a primarily formed N-phenylimine. Alcohol 13b could be readily converted to the corresponding bromide using tetramethyl-α-bromoenamine. The bromide was reacted with the carbanion derived from the protected glycine derivative to yield the diastereomeric fullerene amino acid derivatives 1-benzyl-4-[α-propyl-tert-butylglycinate benzophenone imine] 1,4-dihydro[60]fullerenes 24a and 24b. 相似文献
6.
Two kinds of thio-heterocyclic fused naphthalene carboxamides, 3a-b, 4a-b, were designed, synthesized and quantitatively evaluated as efficient antitumor and DNA photocleaving agents. Compound 3a or 3b, having the thiophene ring, intercalated into DNA more strongly than compound 4a or 4b, having the thioxanthene ring. Compound 4a or 4b, photocleaved DNA more efficiently than 3a or 3b via superoxide anion. Compound 4a was the strongest inhibitor for P388 (murine leukemia cell), while 3a was the most cytotoxic one against A549 (human lung cancer cell). Each new compound showed stronger DNA photocleaving activity than corresponding naphthalimide. 相似文献
7.
Giuseppe BorsatoOttorino De Lucchi Fabrizio FabrisVittorio Lucchini Pietrogiulio FrascellaAlfonso Zambon 《Tetrahedron letters》2003,44(17):3517-3520
The resolution by Lipase PS of rac-5 (from reduction of ketone 6, obtained from dicyclopentadiene with a new environment-friendly synthesis) gives (2S)-5, which was further reduced to the endo(2R)-1a alcohol. The endo(2S)-1b alcohol was obtained from camphor with a multistep synthesis. Pinacol couplings of 3a,b, carried out with Mg/Hg or Corey's general procedure respectively, afforded with high diastereoselectivity the C2 symmetry diols (2R,2′R)-2a and (2S,2′S)-2b, with endo oriented OH functions. The enantiogenic power of the endo alcohol (2R)-1a and (2S)-1b and of the diols (2R,2′R)-2a and (2S,2′S)-2b was tested towards the LiAlH4 reduction of acetophenone. The C2 symmetry appears to play a fundamental role. 相似文献
8.
Jens Högermeier 《Tetrahedron》2007,63(35):8485-8491
We demonstrate in this report that bicyclic alkenyl nonaflates (nonafluorobutanesulfonates) generated from 8-heterobicyclo[3.2.1]octan-3-one derivatives are excellent substrates for Sonogashira couplings with alkynes. Employing CuI, Pd(OAc)2, PPh3 in DMF/i-Pr2NH as standard reagents structurally diverse bicyclic nonaflates were coupled with phenyl acetylene in generally high yields. Particularly efficient are transformations of precursors 16, 18, and 20 bearing methyl groups at the bridgehead carbons, which furnished the expected enynes 17, 19, and 21 in approximately 90% yield. With respect to the alkyne component the scope of this palladium-catalyzed reaction seems also to be fairly broad. Thus, trimethylsilyl acetylene and propargyl alcohol could also be used, affording coupling products 22, 23, and 25 with high efficacy. The protocol of Grieco was applied to induce a domino coupling of tricyclic alkenyl nonaflate 14 with trimethylsilyl acetylene affording product 26 in moderate yield and as 1:1 mixture of the expected two diastereomers. 相似文献
9.
Zhiyong Chen 《Tetrahedron letters》2009,50(46):6398-6401
Stereoselective synthesis of 10 unique bifunctional stereoisomeric adjacent bis-THF intermediates (R = Bz), including 5.1-5.4, 5.7-5.9, 5.11, and 5.15-5.16, of 16 possible compounds, is described. The key steps used in the synthesis of these compounds included the rhenium(VII) oxide-mediated and the Co(modp)2-catalyzed trans oxidative cyclizations (OCs), the OsO4-catalyzed cis OC, and the Williamson’s type etherification reactions. The remaining six bis-THF intermediates (R = Bn) can be prepared from 5.7-5.9, 5.11, and 5.15-5.16 (R = Bz) in two steps, including protection of the free alcohol as benzyl ether followed by the benzoate deprotection. These intermediates should provide access to all 64 asimicin stereoisomers and their analogs. 相似文献
10.
Guido Krämer 《Tetrahedron letters》2009,50(34):4810-4812
(Z)-Cyclodec-1-en-6-yne (3) generates three conjugated hexahydroazulenes 3→1k→1c, 1? under FVP conditions, whereas flash vacuum pyrolysis (FVP) of cyclodecyne (2) leads to 1,2,9-decatriene (9). We attribute the different thermal behavior of 2 (ring opening) and 3 (ring closure) to different transannular interactions. Altogether 22 constitutional isomers of hexahydroazulene should exist; three new isomers (1k, 1?, and 1m) are presented here, ten were described earlier, but the reinvestigation of the dehydration route of bicyclic alcohol 11 showed that one of the ten structures has to be revised. 相似文献
11.
Tris-1,1,1-(hydroxymethyl)ethane 1 was converted to a series of mono- and disubstituted derivatives. An indirect protocol for the differentiation of the alcohol groups was employed for the synthesis of partially and fully differentiated 1 containing a protected aldehyde unit. Complete differentiation of the alcohol groups was also achieved using a direct strategy (two steps from 1). The first synthesis of 1,3-dialdehydes derived from 1 is reported in two steps. 相似文献
12.
Described is the asymmetric synthesis of the allylic alcohols 11 (85% ee), 15 (99% ee), 17 (93% ee), 19 (61% ee), and 21 (69% ee) through a Pd-catalyzed reaction of the unsymmetrical carbonates rac-10, rac-12, rac-14, rac-16, rac-18, and rac-20, respectively, with KHCO3 and H2O in the presence of bisphosphane 6. Similarly the allylic alcohols 23 (99% ee) and 25 (97% ee) have been obtained from the symmetrical carbonates rac-22 and rac-24, respectively. Reaction of the meso-biscarbonate 26 with H2O and Pd(0)/6 afforded alcohol 27 (96% ee), which was converted to the PG building block 32. The unsaturated bisphosphane 33 showed in the synthesis of alcohols 36, 37, and 39 a similar high selectivity as 6. The formation of alcohols 11, 15, and 17 involves an efficient dynamic kinetic resolution. 相似文献
13.
Concise syntheses of the substituted enynediones 28a, 33b and 36 starting from the cyclohexenealdehyde 18, corresponding to ring A in the taxanes, and the vinylstannane 24, are described. Treatment of 36 with Bu3SnH-AIBN did not lead to the oxy-substituted taxadiene 37 expected from a tandem radical macrocyclisation-radical transannulation sequence; instead, a mixture of unidentified products resulted. When the PMB ether 33b corresponding to the alcohol 36 was treated with Bu3SnH-AIBN under similar conditions, p-anisaldehyde was isolated, as a major by-product, but no evidence for the formation of a taxadiene could be observed. In contrast, the iododienynedione 41, i.e., deoxy 36, underwent a tandem radical macrocyclisation-transannulation sequence, when treated with Bu3SnH-AIBN, leading to the tetraoxy-bis-nortaxadiene 42 in 44% yield. Attempts to synthesise the alcohol 28b from the silyl ether 28a en route to the iodide 28c instead gave the substituted tetrahydrofuran 29 via an intramolecular oxy-Michael reaction. 相似文献
14.
Nozomi Saito Toshihiro Matsunaga Miyuki Anzai Daishiro Miura Midori Takimoto-Kamimura 《Tetrahedron》2004,60(36):7951-7961
Novel vitamin D receptor (VDR) antagonists, 24,24-dimethyl-1α-hydroxyvitamin D3-26,23-lactones (8 and 9) and their C2α functionalized analogues (8a-c and 9a-c) were efficiently synthesized and their biological activities were evaluated. The construction of vitamin D3 triene skeleton was achieved by palladium-catalyzed alkenylative cyclization of A-ring precursor enyne (22 and 22a-c) with CD-ring bromoolefin having a 24,24-dimethyl-α-methylene-γ-lactone unit on the side chain (13 and 14). The CD-ring precursors 13 and 14 were prepared by using chromium-mediated allylation of the aldehyde 10 derived from vitamin D2. On the other hand, the A-ring enyne having 2α-(3-hydroxypropyl) group (22b) was newly synthesized from epoxide 15 using regio- and stereoselective alkylation methodology. The potency of the antagonistic activity of the newly designed analogues (8 and 9) increased up to 12 times that of TEI-9647 (2). Furthermore, introduction of the three motifs, that is, a methyl (8a and 9a), an ω-hydroxypropyl (8b and 9b) or an ω-hydroxypropoxyl group (8c and 9c) into the C2α position of 8 and 9, respectively, resulted in remarkable enhancement, up to 89 times, of the antagonistic activity on VDR. 相似文献
15.
Yoshiharu Amano 《Tetrahedron letters》2006,47(37):6505-6507
Oxidation of the methoxyamide derivatives 1, 4, and 7 has been examined to elaborate efficient synthetic methodology of the azacyclic derivatives 2, 3, 5, 6, and 8, which would be applicable as synthetic intermediates of complicated bioactive substances. In addition to direct anodic and PIFA [phenyliodine(III) bis(trifluoroacetate)] oxidations, an active species derived from iodobenzene generated under electrolytic conditions was examined as an oxidant, and its synthetic efficacy was demonstrated in comparison of the reaction outcomes with other oxidation methods. In the oxidation, the methoxy substitution of substrates modulated the cyclization mode to provide the azaspiro- (2, 8) or quinolinone-type (3, 5, 6) products. 相似文献
16.
Markus Ugele 《Tetrahedron》2010,66(14):2633-2641
The alkaloid tyroscherin (2), which contains a vicinal anti-amino alcohol subunit was prepared from 4-hydroxyphenylpropionic acid (5) and meso-diol 9. After desymmetrization of diol 9 and suitable protecting group manipulations, one terminus was extended via a Claisen rearrangement giving rise to enoate ent-15. The missing carbon on the other end could be incorporated using MeMgCl/CuBr·SMe2 leading eventually to aldehyde ent-22. The acylated oxazolidinone 32 derived from acid 5 and aldehyde ent-22 were combined in an aldol reaction. A subsequent Curtius rearrangement on the carboxylic group furnished the amino function of tyroscherin (2). In a proof of concept study the same strategy was used to prepare tyroscherin analog 28. 相似文献
17.
A novel approach for the synthesis of a bird-shaped bis-triquinane 3, a fascinating carbocyclic framework closely related to the skeleton of Xeromphalinone E 1 from readily available 2,6-dimethyl phenol 8 has been reported. The synthesis of bis-cyclohexadienones 6, 22a–e by oxidative acetylation of tetramethyl bisphenols 7, 20a–e has been investigated using two different reagents under varying reaction conditions. The cycloaddition of bis-cyclohexadienone 6 gives two carbocycles, bis-adduct 4b and mono-adduct 5d in a stereocontrolled manner. The photochemical sigmatropic 1,2-acyl shift in 4b furnished 3 and monotriquinane 9 linked with a 9-acetoxy-9-methyl-endo-tricyclo[5,2,2,02,6]undeca-4,10-diene-8-one system. Two different pentasubstituted phenols 13 and 14 were also isolated during an attempted oxa-di-π-methane (ODPM) rearrangement of mono-adduct 5d via aromatisation of the cyclohexadienone ring. The photochemical behaviour of bis-cyclohexadienones 6, 22a–e has also been investigated under UV irradiation and two different aromatized products were isolated for each bis-cyclohexadienone by migration and elimination of acetate groups. 相似文献
18.
Masayoshi Tsubuki 《Tetrahedron》2005,61(5):1095-1100
Wittig rearrangement of 17(20)-ethylidene-16-furfuryloxy steroids 5-8 was examined. Reaction of 17E(20)-ethylidene-16α-furfuryloxy steroid 5 with t-BuLi in THF afforded (20S,22S)- and (20S,22R)-22-hydroxy steroids 9, 10 and 17Z(20)-ethylidene-16α-(2-furyl)hydroxymethyl steroid 11 in 61, 28, and 9% yields, respectively. Base treatment of 17E(20)-ethylidene-16β-furfuryloxy steroid 7 gave (20R,22R)-22-hydroxy steroid 13 and 17Z(20)-ethylidene-16β-(2-furyl) hydroxymethyl steroid 14 in 60 and 17% yields. In contrast, 17Z(20)-ethylidene-16-furfuryloxy steroids 6, 8 led to the corresponding 2,3-rearranged products in low yields (25% for (20R,22S)-22-hydroxy steroid 12; 31% for (20S,22R)-22-hydroxy steroid 10). Both (20S,22S)- and (20S,22R)-22-hydroxy steroids 9, 10 were converted by catalytic hydrogenation into known compounds 16, 17, key intermediates for the synthesis of biologically active steroids. 相似文献
19.
Nicolas Zorn 《Tetrahedron letters》2006,47(26):4325-4330
The stereospecific synthesis of the dienophile subunits 5 was achieved from the butenolide 6. Ester 19 was obtained in 67% overall yield (2 steps), with no intermediate purification, by a sodium chlorite oxidation of the corresponding aldehyde in buffered conditions, followed immediately after extraction, by a Mitsunobu reaction of the relatively labile acid 3 with alcohol 13. The synthesis of the α,β-unsaturated aldehydes 22 and 23 is also reported. Tentative IMDA reactions of 22 and 23 were examined in thermal conditions, or with a Lewis acid catalysis, and results are reported herein. 相似文献
20.
The synthesis of a series of new alkoxylated linearly annulated dioxins is described together with their cyclic voltammetric behavior and some preliminary result on their ability to form cation radical salts. Of these dioxins, seven (8, 12, 19, 21, 27, 33, 34) are the first representatives of entirely new heterocyclic systems. Dioxins 8, 21, 22 and 27 gave good quality cation radical salts upon electrocrystallization. 相似文献