Total efficiency

Catalytic hydrogenation of the 14—15 double bond from the face opposite to the C18 substituent yields (196). Compound (196) contains the natural steroid stereochemistry around the D-ring. A metal-ammonia reduction of (196) forms the most stable product (197) thermodynamically. When R is equal to methyl, this process comprises an efficient total synthesis of estradiol methyl ester. Birch reduction of the A-ring of (197) followed by acid hydrolysis of the resultant enol ether allows access into the 19-norsteroids (198) (204). 

Other, removable cation-stabilizing auxiliaries have been investigated for polyene cyclizations. For example, a sdyl-assisted carbocation cyclization has been used in an efficient total synthesis of lanosterol. The key step, treatment of (257) with methyl aluminum chloride in methylene chloride at —78° C, followed by acylation and chromatographic separation, affords (258) in 55% yield (two steps). When this cyclization was attempted on similar compounds that did not contain the C7P-silicon substituent, no tetracycHc products were observed. Steroid (258) is converted to lanosterol (77) in three additional chemical steps (225). 

An illustrative example of the potency of the second-generation Ru catalyst C is found in Paquette s highly efficient total synthesis of the natural products teubrevin G (122) and teubrevin H (123), which feature a cyclooctane core fused and spiroannulated to smaller oxygen-containing rings [76]. In the retrosyn-thetic analysis, the viability of an RCM step for annulation of a cyclooctenone ring to the furan played a central role. 

Cold finger refrigerant traps are often used in vacuum lines as a substitute for the more efficient total immersion traps which, however, tend to cut down the pumping speed of the system. In constructing a cold finger trap a Dewar seal is first made, then, before... 

Zhang, C. TrndeU, M.L. (1996) A Short and Efficient Total Synthesis of ( )-Epibatidine. Journal of Organic Chemistry, 61, 7189-7191. 

Kobayashi, S., Ueda, T, Fukuyama, T. (2000) An Efficient Total Synthesis of (—)-Vindoline. Synlett, 883-886. 

In the same area, a (5)-tryptophan-derived oxazaborolidine including a p-tolylsulfonylamide function has been used by Corey et al. to catalyse the enantioselective Diels-Alder reaction between 2-bromoacrolein and cyclo-pentadiene to form the corresponding chiral product with an unprecedented high (> 99% ee) enantioselectivity (Scheme 5.27)." This highly efficient methodology was extended to various 2-substituted acroleins and dienes such as isoprene and furan. In addition, it was applied to develop a highly efficient total synthesis of the potent antiulcer substance, cassiol, as depicted in Scheme 5.21... 

Jackson HL, Nadolski GT, Braun C, and Lockwood SF. 2005. Efficient total synthesis of lycophyll (v /, /-carotene-16,16 -diol). Organic Process Research Development 9(6) 830-836. 

The described procedure has been widely used by Smith III and coworkers [250] in the efficient total synthesis of natural products containing extended 1,3-hydroxylated chains. This architecture is often found as a structural element in polyene macrolide antibiotics [251] such as mycotoxin A and B, dermostatin, and roxaticin. The Smith group used the above-mentioned approach (e. g., as five-component coupling) for the synthesis of the pseudo-C2-symmetric trisacetonide (+)-2-471 [252], which was employed by Schreiber and coworkers [253] within the synthesis of (+)-mycotoxin A (2-470a) (Scheme 2.108). Thus, lithiation of 2.5 equiv. dithiane 2-462b followed by treat-... 

During the course of a short and efficient total synthesis of (-) -dendrobine (3-76), an alkaloid which exhibits antipyretic and hypotensive activities [37], a new domino radical sequence has been exploited by Cassayre and Zard which involves the cycli-... 

Having an efficient total synthesis of the indole alkaloid vindoline in mind, the Boger group [47] developed a facile entry to its core structure using a domino [4+2]/[3+2] cycloaddition. Reaction of the 1,3,4-oxadiazoles 4-139 led to 4-140 in high yield and excellent stereoselectivity via the intermediates 4-141 and 4-142 (Scheme 4.29). 

A retro-l,3-dipolar cycloaddition followed by an 1,3-dipolar cycloaddition was used for a highly efficient total synthesis of (-)-histrionicotoxin (4-354) (HTX) by Holmes and coworkers [123]. HTX is a spiropiperidine-containing alkaloid which was isolated by Doly, Witkop and coworkers [124] from the brightly colored poison-arrow frog Dendrobates histrionicus. It is of great pharmacological interest as a noncompetitive inhibitor of acetylcholine receptors. 

Bergeron RJ, McManis JS, Dionis JB, Garlich JR (1985) An Efficient Total Synthesis of Agrobactin and its Ga(III) Chelate. J Org Chem 50 2780... 

Fiirstner A, Muller T (1999) Efficient Total Syntheses of Resin Glycosides and Analogues by Ring-Closing Olefin Metathesis. J Am Chem Soc 121 7814... 

DOS seems mainly important for lead identification. Based on the lead structure, additional structural complexity can be introduced in a direct manner by generating focused libraries. For the synthesis of complex molecules, total synthesis as it exists today and the development of selective reactions that accompany, it remain of major importance. Even in case of the successful identification of advanced leads or drug candidates from DOS, an efficient total synthesis is always required in order to provide sufficient amounts of a limited set of derivatives for detailed medicinal chemistry studies up to clinical trials. 

Boger has reported efficient total syntheses of the marine alkaloids ningalin A, lamellarin O, lukianol A, and stomiamide A each of which possess a common 3,4-diaryl-substituted pyrrole nucleus bearing 2- or 2,5-carboxylates <99JA54>. A key step in each of these syntheses utilized a zinc mediated reductive ring contraction of 1,2-diazines such as 29 to pyrrole 30, a precursor in... 

Duration FM DM Productivity Productivity Efficiency (Total) Efficiency (Tuber)... 

Although the tetracycline antibiotics have been mainstays of antibacterial chemotherapy for decades, they had eluded efficient total synthesis. In a landmark accomplishment, Andrew G. Myers of Harvard University recently reported (Science 2005,308, 395 J. Am. Chem. Soc. 2005, 127, 8292) the first such syntheses. 

Despite the fact that the [4 + 2] cycloaddition strategy was intriguing and novel, it posed serious limitations in achieving an efficient total... 

We describe herein our recent achievement of total syntheses of (-)-strychnine and fostriecin. The key stereocenters were constructed using catalytic asymmetric reactions developed in our group. Catalytic asymmetric reactions that can produce versatile chiral building blocks with high practicality should ensure further efficient total synthesis of complex molecules in future. 

Kotoku N, Tsujita H, Hiramatsu A, Mori C, Koizumi N, Kobayashi M (2005) Efficient Total Synthesis of Bastadin 6, an Anti-Angiogenic Brominated Tyrosine-Derived Metabolite from Marine Sponge. Tetrahedron 61 7211... 

Since every system under consideration is subject to different efficiency, it is of interest to have efficiency as the integral parameter of the system which comprises element characteristics of the system. The performance indicator in this assessment procedure is composed of number of sub-indicators efficiency, total energy cost, capital cost and lifetime. The efficiency of the system is considered as the integral parameter for the performance validation. The total energy cost is result of the system optimization with minimum energy cost constrain. The capital cost is a measure of the investment per unit energy produced in the lifetime of the system. Also, the important parameter in the assessment of performance of the energy system is the lifetime of system. 

Concise and efficient total synthesis of Lycopodium alkaloid magellanine. Angewandte Chemie, International Edition, 41 (21), 4090 1093. 

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