Stereocontrolled total synthesis

Compound A was also made by a direct, stereocontrolled total synthesis (Ref. 4). 

Stepwise, Stereocontrolled Total Synthesis of Endiandric Acids A-D (and E-G)... 

In a versatile stereocontrolled total synthesis of (+)-vinblastine, Fukuyama used a base-promoted macrocyclization of the N-nosylate and the terminal epoxide moiety present in 88 as one of the key steps, giving the 11-membered-ring product 89 in 82% yield (Scheme 8.23) [42],... 

More recently, the same group achieved a simple, highly stereocontrolled total synthesis of (+)-hirsutic acid (Scheme LXXIX) ". This chirally directed effort developed subsequent to reaction of dl-728 with (+)-di-3-pinanylborane, alkaline hydrogen peroxide oxidation, chromatography, PCC oxidation, and hydrogenolysis. The dextrorotatory hydroxy ketone 729 was nicely crafted into keto aldehyde 730 from which 720 was readily obtained. Once again, the Wacker oxidation played an instrumental role in annulation of the third five-membered ring. The remainder of the asymmetric synthesis was completed as before. 

As part of on going efforts of Williams and his coworkers [46] to elucidate the biosynthesis of the core bicyclo[2.2.2] ring system of the related alkaloids the brevianamides [51], they have applied methodology originally developed for the stereocontrolled total synthesis of (-)-brevianamide B [52] to complete the first stereocontrolled total synthesis of (+)-PHB. 

Paterson I, Florence GJ, Heimann AC, Mackay AC (2005) Stereocontrolled Total Synthesis of (-)-Aurisides A and B. Angew Chem Int Ed 44 1130... 

An elegant and efficient stereocontrolled total synthesis of strychnine has been achieved by applying intramolecular Diels Alder and Heck reations as key reactions [47]. An unusual exo-Diels-Alder reaction of 102 afforded 103, which was converted to the vinyl iodide 104. The Heck reaction of 104 using Pd(OAc)2 gave the hexacyclic strychnan system 105 smoothly in 74% yield. Hydrolysis of 105 afforded isostrychnine, which was isomerized to strychnine (106) under basic conditions. 

The first highly stereocontrolled total synthesis of a natural penicillin was reported 2 years later by Baldwin et al. <1976JA3045>. In this case, the methodology relies on the formation of the fi-lactam ring before the thiazolidine ring closure, via the sulfenic acid intermediate 97 (Rz = OH), which gives electrophilic attack on the double bond to produce a penam sulfoxide 98 (see Section 2.03.5.3) (Scheme 52). A similar route has been developed independently by Kishi for the total synthesis of 6cr-methoxy penicillin derivatives <1975JA5008>. 

A bioxantracene (-)-ES-242-4 (46) was isolated from the culture broth of Verticillium sp. in 1992 as one of eight antagonists for the 7V-methy 1-D-aspartate (NMDA) receptor (7<5). These novel natural products are reported to inhibit the PH]thienyl cyclohexylpiperidine binding to rat crude synaptic membranes, and therefore, are of potential therapeutic interest for die treatment of neurodegenerative diseases. (-)-ES-242-4 (46) is structurally remarkable having an axially chiral binaphthalene core that is adorned with two pyrans of the same absolute chirality. Our interest in the construction of densely functionalized naphthopyran ring systems, via tandem Michael-Dieckmann reactions, promoted us to attempt the first stereocontrolled total synthesis of (-)-ES-242-4 (46) (19). 

A highly enantio- and diastereoselective hDA reaction between substituted hexadiene 1033 and aldehydes is catalyzed by Jacobsen s chiral tridentate chromium(m)-catalyst 1034 furnishing tetrahydropyran-4-ones 1035 (Equation 401, Table 48) <1999AGE2398>. This methodology is incorporated into a stereocontrolled total synthesis of (+)-leucascandrolide A <2003AGE343> and the synthesis of the C(20)-C(32) segment of the phorboxazoles... 

Samajdar, S., Ghatak, A., and Ghosh, S. (1999) Stereocontrolled total synthesis of ( )-fS -necrodol. Tetrahedron Letters,... 

Ref. 4 in Wakamatsu K, Kigoshi H, Niiyama K, Niwa H, Yamada K (1984) Stereocontrolled Total Synthesis of (+)-Asteromurin A, a Picrotoxane Sesquiterpene Isolated from the Scale Insect Asterococcus muratae Kuwana. Chem Lett 1763... 

Corey EJ, Pearce HL (1979) Total Synthesis of Picrotoxinin. J Am Chem Soc 101 5842 Niwa H, Wakamatsu K, Hida T, Niiyama K, Kigoshi H, Yamada M, Nagase H, Suzuki M, Yamada K (1984) Stereocontrolled Total Synthesis of (—)-Picrotoxinin and (-i)-Coriamyrtin via a Common Isotwistane Intermediate. J Am Chem Soc 106 4547 Miyashita M, Suzuki T, Yoshikoshi A (1989) Selective Total Synthesis of (—)-Picrotoxinin and (—)-Picrotin. J Am Chem Soc 111 3728... 

Tanaka K, Uchiyama F, Sakamoto K, Inubushi Y (1982) Stereocontrolled Total Synthesis of ( )-Coriamyrtin. J Am Chem Soc 104 4965... 

Lee CH, Westling M, Livinghouse T, Williams AC (1992) Acybiitrilium Ion Initiated Heteroannulations in Alkaloid Synthesis. An Efficient, Stereocontrolled, Total Synthesis of Orchidaceae Alkaloid ( )-Dendrobine. J Am Chem Soc 114 4089... 

Niwa H, Yamada K (1986) Stereocontrolled Total Synthesis of Picrotoxane Sesquiterpe-noids. J Syn Org Chem (Japan) 44 180... 

Xu, X.-X. Zhu, J. Huang, D.-Z. Zhou, W.-S. Studies on the structure and synthesis of arteannuin and related compound XVII. The stereocontrolled total synthesis of methyl dihydroarteannuate—the total synthesis of arteannuin. Huaxue Xuebao, 1984, 42 940-942. 

A highly stereocontrolled total synthesis of the cytotoxic 18-membered macrolide (-H)-leucascandrolide A has been reported <03T6833> as well as the second total synthesis of... 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

Intramolecular Heck substitution reactions have been key steps in several recent synthetic endeavors directed toward Strychnos alkaloids (Scheme 6-11). In 1993, Rawal and coworkers reported a short stereocontrolled total synthesis of ( )-dehydrotubifoline (62) in which vinyl iodide 61 was converted to pentacycle 62 in good yield using Jeffery s cyclizatioti conditions [22]. Of note in this construction of the core pentacyclic skeleton of... 

Our work on fluorenones and alkaloids was extended to design convenient, expeditious and stereocontrolled total synthesis of several naturally occuring diterpenoids [55] namely ( )-ferruginol (5), ( )-nimbidiol (6), ( )-nimbiol (7), ( )-totarol (8) and abietatriene (9) (Schemes 4-8) via a concerted mechanism of domino acylation-cycloalkylation/ alkylation-cycloacylation as the principal step to construct the basic carbocyclic framework required for the trans-fused... 

The critical step in the enantioselective and stereocontrolled total synthesis of eunicenone A by E.J. Corey et al. was the highly efficient chiral Lewis acid catalyzed intermolecular Diels-Alder cycloaddition reaction The diene component was mixed with 5 equivalents of 2-bromoacrolein and 0.5 equivalents of the chiral oxazaborolidine catalyst in CH2CI2 at -78 °C for 48h. The reaction gave 80% of the desired cycloadduct in 97% ee and the endolexo selectivity was 98 2. 

The key step in the stereocontrolled total synthesis of the tricyclic (+)-kelsoene by M. Koreeda et al. was a base-catalyzed homo-Favorskii rearrangement of a y-keto tosylate to elaborate the 4-5 fused ring portion of the target molecule. The bicyclic 5-6 fused y-keto tosylate was treated with excess potassium fert-butoxide, which effected the desired rearrangement in less than 2 minutes at room temperature. The nucleophilic solvent was too bulky to effect the opening of the cyclobutanone intermediates, making their isolation possible. The mixture of isomeric cyclobutanones was converted to a separable 1 1 mixture of cyclobutanones with p-TsOH, and the ketone functionality was then removed via the corresponding tosylhydrazone. 

A convergent, stereocontrolled total synthesis of the microtubule-stabilizing macrolides, epothilones A and B was achieved in the iaboratory of S.J. Danishefsky. During their investigations, they examined several approaches to construct these natural products. One possible strategy to introduce the Cl 5-hydroxyl group in an enantioselective fashion was to use Keck s asymmetric allylation method. Under standard conditions, the reaction provided the desired homoallylic alcohol in good yield and excellent enantioselectivity. 

The stereocontrolled total synthesis of (-)-macrolactin A, a 24-membered macrolide, was achieved by J.P. Marino and co-workers/ The key macrocyclization step was carried out using the Yonemitsu modification of the Yamaguchi macroiactonization. In this procedure, the mixed anhydride is added to the highly dilute solution of DMAP rapidly (in one portion) at room temperature. The final step of the total synthesis was the removal of the protecting groups under acidic condition. 

Nicolaou, K. C., Petasis, N. A., Uenishi, J., Zipkin, R. E. The endiandric acid cascade. Electrocyclizations in organic synthesis. 2. Stepwise, stereocontrolled total synthesis of endiandric acids C-G. J. Am. Chem. Soc. 1982, 104, 5557-5558. 

Xu, Y.-C., Kohiman, D. T., Liang, S. X., Erikkson, C. Stereoselective, Oxidative C-C Bond Coupling of Naphthopyran Induced by DDQ Stereocontrolled Total Synthesis of Deoxyfrenolicin. Org. Lett. 1999,1,1599-1602. 

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