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1.
Shu C Zeng X Hao MH Wei X Yee NK Busacca CA Han Z Farina V Senanayake CH 《Organic letters》2008,10(6):1303-1306
We report here that dramatic improvement of the key RCM reaction in the synthesis of HCV protease inhibitor BILN2061 can be achieved by N-substitution of the diene substrate with an electron-withdrawing group. Mechanistic studies using 1H NMR spectroscopy showed an unprecedented switch of the initiation sites and the correlation between such switch and the results of RCM, from the unmodified to the modified substrates. We also provided theoretical evidence that such modification may also increase the thermodynamic preference of the macrocyclic product over the diene substrate. 相似文献
2.
Faucher AM Bailey MD Beaulieu PL Brochu C Duceppe JS Ferland JM Ghiro E Gorys V Halmos T Kawai SH Poirier M Simoneau B Tsantrizos YS Llinàs-Brunet M 《Organic letters》2004,6(17):2901-2904
The synthesis of BILN 2061, an NS3 protease inhibitor with proven antiviral effect in humans, was accomplished in a convergent manner from four building blocks. The procedure described here was suitable for the preparation of multigram quantities of BILN 2061 for preclinical pharmacological evaluation. 相似文献
3.
Kong J Chen CY Balsells-Padros J Cao Y Dunn RF Dolman SJ Janey J Li H Zacuto MJ 《The Journal of organic chemistry》2012,77(8):3820-3828
A highly efficient synthesis of Vaniprevir (MK-7009) has been accomplished in nine linear steps and 55% overall yield. The key features of this synthesis include a cost-effective synthesis of the isoindoline subunit and efficient construction of the 20-membered macrocyclic core of Vaniprevir (MK-7009) utilizing ring-closing metathesis technology. A high-performing ring-closing metathesis protocol has been achieved by simultaneous slow addition of the ruthenium catalyst (0.2 mol %) and the diene substrate at a concentration of 0.13 M. 相似文献
4.
M J?rgensen E H Iversen A L Paulsen R Madsen 《The Journal of organic chemistry》2001,66(13):4630-4634
Two short synthetic approaches to enantiopure conduritols are described starting from the chiral pool. In both cases, the cyclohexene ring is assembled via ring-closing olefin metathesis. The terminal diene precursers for the metathesis reaction are prepared either from octitols or from tartaric acids. The former route involves a new method for selective bromination of the primary positions in long-chain carbohydrate polyols. Subsequent reductive elimination with zinc then generates the diene. The latter route uses a highly diastereoselective addition of divinylzinc to tartaric dialdehydes for preparation of the dienes. 相似文献
5.
Velázquez F Venkatraman S Wu W Blackman M Prongay A Girijavallabhan V Shih NY Njoroge FG 《Organic letters》2007,9(16):3061-3064
An efficient synthetic approach for the preparation of macrocyclic peptidomimetics for inhibition of HCV NS3 is presented. The macrocyclic core is built using ring-closing metathesis (RCM) of a tripeptidic diene. The presented approach allows the introduction of heteroatoms in strategic places along the macrocyclic ring. The methyl ester moiety in the RCM products was synthetically manipulated to install a keto-amide moiety via a Passerini reaction. 相似文献
6.
A highly convergent stereoselective total synthesis of aspinolide B, a 10-membered lactone is described. The key step includes a ring-closing metathesis reaction to construct the 10-membered ring and the E—olefinic moiety. d-Mannitol was used as a chiral pool material for the construction of the key fragments—the olefinic acid and the olefinic alcohol moieties. 相似文献
7.
Vincent Chaleix 《Tetrahedron letters》2004,45(27):5295-5299
We report the efficient solid-phase synthesis of a new family of peptidic porphyrins containing a constrained RGD moiety obtained by ring-closing metathesis. 相似文献
8.
Ring-closing metathesis reactions of para-disubstituted aromatic substrates produced macrocyclic [n.n]-, and [n.n.n]paracyclophanes efficiently through dimerization and trimerization reactions. Sufficiently long alkyl chains allowed direct monocyclizations to yield [n]paracyclophanes. A small library of paracyclophanes were generated by the combinatorial cross-metathesis approach. 相似文献
9.
《Tetrahedron: Asymmetry》2006,17(23):3197-3202
Stereoselective synthesis of diplodialides-B and C and the formal synthesis of diplodialide-A are reported. A combination of Jacobsen’s hydrolytic kinetic resolution and Sharpless epoxidation is used for the creation of two stereogenic centers, while a ring-closing metathesis strategy was used for the construction of the lactone ring. 相似文献
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11.
The ring-closing enyne metathesis reaction of alkyl 2-substituted-2-(N-alkynyl acrylamido)esters using the first-generation Grubbs’ catalyst afforded five-membered lactams bearing a 1,3-diene moiety in high isolated yields. In the reaction process, the presence of ethylene gas is essential. 相似文献
12.
A short and efficient RCM route is reported for the construction of the key nine-membered B ring of eleutherobin starting from the readily available 1,2,5,6-diisopropylidene-d-glucose. 相似文献
13.
A simple and efficient approach to the synthesis of five-membered ring carbasugars is achieved starting from readily available (R)-2,3-O-isopropylideneglyceraldehyde (2) through key ring-closing metathesis (RCM) in high overall yield. We have also confirmed its viability by preparing the core bicyclo [3.1.0] hexane framework presented in the potent antiviral nucleoside N-MCT 1. 相似文献
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15.
A concise route to a key intermediate in the total synthesis of guanacastepene A is described. The main features include the simultaneous construction of the seven- and six-membered rings, using a tandem ring-closing metathesis and a stereoselective introduction of the oxygenated function at the C5 position. [reaction: see text] 相似文献
16.
An asymmetric formal total synthesis of diplodialide A 1a has been achieved starting from methyl acetoacetate 6 and (R)-3-buten-2-ol 7. The macrocyclic ring core of (+)-diplodialide A 1a was constructed, in an excellent yield, by using a ring-closing metathesis strategy. 相似文献
17.
[reaction: see text] A new total synthesis of macrosphelides A and B using ring-closing metathesis (RCM) as a macrocyclization step is described. The substrate of the RCM could be synthesized from readily available chiral materials, methyl (S)-(+)-3-hydroxybutyrate and methyl (S)-(-)-lactate, with a high efficiency. The RCM proceeded in the presence of Grubbs' Ru-complex, providing a new effective synthetic route to these natural products. 相似文献
18.
[reaction: see text] A series of new pyrrolidine derivatives were prepared directly in very good yields, from the substrates containing a basic or nucleophilic N atom via ring-closing enyne metathesis reaction under mild reaction conditions. Moreover, the reaction occurs smoothly without the presence of ethylene gas. 相似文献
19.
[Structure: see text] Described is a regio- and stereoselective ring-closing metathesis (RCM) to form the C2-C3 alkene of the macrolide-containing domain of phorboxazole A. This work demonstrates a dramatic effect of reaction solvent on RCM product (E/Z)-selectivity. This process offers an alternative assembly of the macrolide-containing domain of phorboxazole A, one of the most potent anticancer agents known. 相似文献