Formal Total Syntheses of the β-Lactam Antibiotics Thienamycin and PS-5

Jacobi, Peter A.; Murphree, S. Shaun; Rupprecht, Frederic; Zheng, Wanjun

doi:10.1021/jo952092u

Cited by 60 publications

(58 citation statements)

References 64 publications

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“…In addition, we observed for the first time significant formation of a side product in which the BOC group had been cleaved. Jacobi55 has made note of strong solvent effects for the hydrolysis of similar compounds. When we applied new mixed solvent hydrolysis conditions based on the Jacobi observations (LiOH, H 2 O 2 , THF, DMF, H 2 O) we saw an increase in the yield of carboxylic acid 57 , and a subsequent reduction in the amount of BOC cleavage; however, the overall yield of the reaction was still variable.…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions

et al. 2008

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Studies leading to a total synthesis of Epothilones B and D are described. The overall synthetic plan was based on late stage fragment assembly of two segments representing C 1 -C 9 and C 10 -C 21 of the structure. The C 1 -C 9 fragment was prepared by elaboration of commercially available (2R)-3-hydroxy-2-methylpropanoate at both ends of the three carbon unit. Introduction of carbons 1-4 containing the gem-dimethyl unit was achieved in a convergent manner using a diastereoselective addition of a stannane equivalent of a β-keto ester dianion. An enantioselective addition of such a stannane equivalent for a β-keto ester dianion was also used to fashion one version of the C 10 -C 21 subunit; however, the fragment assembly (using bimolecular esterification followed by ring-closing metathesis) with this subunit failed. Therefore, fragment assembly was achieved using a Wittig reaction; this was followed by macrolactonization to close the macrocycle. The C 10 -C 21 subunit needed for this approach was prepared in an efficient manner using the Corey-Kim reaction as a key element. Other key reactions in the synthesis include a stereoselective SmI 2 reduction of a β-hydroxy ketone and a critical opening of a valerolactone with aniline which required extensive investigation.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions

et al. 2008

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“…The initial assumption was that alkylation of 65 at the C-11 position would occur from the convex face of the ring, which turned out to be wrong. Methylation of 65 followed by aldol condensation with the four carbon aldehyde 34 gave the wrong stereoisomer and eventually led to isoallocyathin B 2 (72) (Scheme 11). 35 After considerable experimentation, it was discovered that the desired diketone 75 could be prepared by methylation of diketone 74, the product of C-acylation of ketone 65.…”

Section: Tori's Synthesismentioning

confidence: 99%

Enantioselective Total Synthesis of Cyathin A₃.

Ward

Shen

2007

ChemInform

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The cyathins are a unique group of diterpenoids produced by the bird's nest fungi Cyathus helenae, C. africanus, and C. earlei In Section 2.2, the enantioselective Diels-Alder reaction of quinone 106 and diene 105 is presented. This reaction is effectively catalyzed by a carefully iii prepared Mikami catalyst. It was carried out on a preparative scale to give the chiral building block 108. The absolute configuration of the Diels-Alder adduct 108 was determined by NMR and X-ray analysis.

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“…± The cyclohexenes 8 [53] [54] and 9 [55] were prepared by Curtius rearrangement of commercial cyclohex-3-enecarboxylic acid and treatment of the resulting isocyanate with t-BuOH and CuCl [56] or with CF 3 COOH [55]. This onepot procedure yielded 92% of 8 and 84% of 9 3 ) (Scheme 2).…”

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confidence: 99%

“…Curtius rearrangement of the monoacid 10 and treatment of the resulting isocyanate with t-BuOH and CuCl [56] gave the b-amino-acid derivative 11 (90%), which was reduced to the alcohol 12 (74%). Treating the dianion of 12 with 1.0 equiv.…”

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confidence: 99%

Electrophilic Bromination of N‐Acylated Cyclohex‐3‐en‐1‐amines: Synthesis of 7‐Azanorbornanes

Kapferer

Vasella

2004

Helvetica Chimica Acta

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The intramolecular bromo-amidation and the dibromination-cyclisation of the N-acylcyclohex-3-en-1-amines 4, 8, 9, 11, 13, 14, and 16 was studied in view of the synthesis of bicyclic amines that are of interest as building blocks and potential glycosidase inhibitors. The trifluoroacetamides 4, 9, and 14 reacted with Nbromosuccinimide (NBS) in AcOH to give dihydro-1,3-oxazines in good yields. The stereoselectivity of the dibromination of the alkenes 8 and 9 depends on the nature of the protecting group, the reagent, and the reaction conditions. Br 2 in CH 2 Cl 2 transformed the alkenes 8 and 9 predominantly into diaxial trans,transdibromides. Bromination of 9 with PhMe 3 NBr 3 or with Br 2 in the presence of Et 4 NBr gave predominantly the diequatorial trans,cis-27 besides some trans,trans-28. A similar bromination of the C(5)-substituted N-acyl-4-aminocyclohexenes 11, 13, 14, and 16 with PhMe 3 NBr 3 was accompanied by intramolecular side reactions that were suppressed by the addition of excess Et 4 NBr. Under these conditions, 11 gave diastereoselectively transdibromides, while its reaction with Br 2 gave trans-dibromides along with the dihydrooxazinone 31. Also the carbamate 13 reacted with PhMe 3 NBr 3 /Et 4 NBr selectively to the trans-dibromide 32 and with Br 2 to the transdibromides 32 and 33, the dihydrooxazinone 34, and the bicyclic ether 35. Similarly, the trifluoroacetamide 14 provided the dibromide 36 (89%), while its reaction with Br 2 led to the dihydrooxazine 22, and the dibromides 36 and 37. The N-benzyl-N-Boc derivative 16 did not yield any dibromide; it reacted with PhMe 3 NBr 3 /Et 4 NBr to the dihydrooxazinone 38, and with Br 2 to the oxazinone 38 and the bicyclic ether 39. The high stereoselectivity of the bromination with PhMe 3 NBr 3 /Et 4 NBr suggests an anchimeric assistance of the NHR substituent. Deprotection, cyclisation, and carbamoylation transformed the dibromides 27, 29, and 32 into the 7-azanorbornanes 42, 49, and 53. The diols 45 and 57 were obtained from 42 and 53 via HBr elimination and stereoselective dihydroxylation; they proved weak inhibitors of several glycosidases. In no case could the formation of a bicyclic azetidine (6-azabicyclo[3.1.1]heptane) from the dibromides 26 and 30 be observed.

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Formal Total Syntheses of the β-Lactam Antibiotics Thienamycin and PS-5

Cited by 60 publications

References 64 publications

Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions

Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions

Enantioselective Total Synthesis of Cyathin A₃.

Electrophilic Bromination of N‐Acylated Cyclohex‐3‐en‐1‐amines: Synthesis of 7‐Azanorbornanes

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Formal Total Syntheses of the β-Lactam Antibiotics Thienamycin and PS-5

Cited by 60 publications

References 64 publications

Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions

Total Synthesis of Epothilones B and D: Stannane Equivalents for β-Keto Ester Dianions

Enantioselective Total Synthesis of Cyathin A3.

Electrophilic Bromination of N‐Acylated Cyclohex‐3‐en‐1‐amines: Synthesis of 7‐Azanorbornanes

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Enantioselective Total Synthesis of Cyathin A₃.