Syntheses of racemic

Total syntheses of racemic Melinonine E (316) and Strychnoxanthine (317) were performed using a radical cyclization process as the key step (98JOC968). Melinonine E was first isolated from the bark of Strychnos melinoniana in 1957 (57HCA1167), but structure elucidation was not carried... 

The first cyclization of a-hydroxyalkoxyallenes goes back to the pioneering experiments of Brandsma, Hoff and Arens, who found that dihydrofuran derivatives 102 are formed by treatment of 101 with KOtBu in DMSO (Scheme 8.26) [12c], This reaction protocol was successfully applied by others [61, 63, 64, 80-83], for example in the preparation of spiro compound 104 (Eq. 8.19) [83] and in the cyclization of 64 leading to a-amino acid-derived dihydrofurans 105 (Scheme 8.27) [61, 63], Acidic hydrolysis of dihydrofurans furnished 3(2H)-dihydrofuranones, which could be used again as carbonyl components in the repetitive addition of lithiated methoxyal-lene 42. This concept was employed in syntheses of racemic [82] and enantiomeri-cally pure [64] primary helical spirocycles. 

Scheme 21 Syntheses of racemic and chiral forms of the lactol pheromone of Biprorulus bibax [111]...

Lycorine is the most abundant alkaloid in plants of the Amaryllidaceae. Several syntheses of racemic lycorine had been reported prior to our initiation of studies directed at an asymmetric synthesis of the unnatural enantiomer 64. 2 a common theme in all of the syntheses of ( )-lycorine has been the utilization of either an intermolecular or intramolecular Diels-Alder construction of the key C-ring of the alkaloid. This six-membered ring presents a rather formidable synthetic challenge because of the four contiguous stereogenic centers, the trans 1,2-diol moiety, and the juxtaposition of the aromatic substituent and the carbon-carbon double bond. 

Scheme 5.236). The same route was applied to the syntheses of racemic K-252a and non-natural (—)-K-252a from the DMB-protected aglycon 1381 and the carbohydrates ( + )-1398a,b/( )-1399 and (+)-1398a,b/(—)-1399 as precursors... 

The first, and one of the most straightforward, syntheses of racemic 69 was that of Schach von Wittenau and Els ° after they had determined the stmcmre. Friedel-Crafts alkylation of indole with ethyl 2,3-epoxybutyrate gave the a-indolmycenic acid ester 119a. Cyclization of 119a with Af,//-dimethylguanidine yielded both 69 and isoindolmycin 120 (Scheme 6.32). In this case, facile epimerization of H-5 had occurred under the basic cyclization conditions. 

After the syntheses of racemic doubly bridged [8][8]- and [8][10]paracyclophanes (32 and 33) with D2- and C2-symmetry respectively 6o), the optically active compounds... 

To date, the reported nonphotochemical syntheses of racemic and enantiopure [w helicenes are limited to n = 9 and 8, respectively [62, 63], Recently, asymmetric syntheses of [njhelicenes with n up to 11 were developed in our laboratory [64]. 

Two syntheses of racemic 2,3-dihydrotriquinacen-2-one (380) have been described. The first approach consisted in the selective monoketalization of diketone 364 with 2,2-dimethylpropane-l, 3-diol and Baeyer-Villiger oxidation of 375 (Scheme 60).357 Although two lactones were produced, 376 could be freed of its isomer by selective alkaline hydrolysis. Diisobutylalumium hydride reduction of 376 afforded 377, the acetate of which was converted by acid treatment to 378. Ketaliza-tion of this isomeric mixture, followed by hydrolysis, mesylation, and treatment with potassium f-butoxide in dimethyl sulfoxide afforded diene ketal 379. Deketa-lization then liberated the desired ketone. 

Several syntheses of racemic salsolinol (64) by Pictet-Spenglercycliza-tion of dopamine with acetaldehyde have been reported 10a,150). The synthesis of the optically active (5) enantiomer TIQ 64a from the methyl ether analogs TIQs 62a and 68a by acid hydrolysis correlates the chemistry of mammalian alkaloids with that of plant isoquinolines (146-148). 

Interesting syntheses of racemic sativene (203), copacamphene (205), cis-sativenediol (206), and helminthosporal (207) have been reported (Scheme 32). " The key step at the start of these syntheses is the acid-catalysed thermal rearrangement of (201), which is obtained by photolysis of piperitone in 1,1-dimethoxyethane, to give the two epimeric ketones (202). These two epimers are... 

Two syntheses of racemic betalamic acid have been carried out so far. In Dreiding s approach (Scheme 1) (11,90,91), chelidamic acid (62) was used as the starting material. Hydrogenation of 62 with a rhodium catalyst yielded an all-cw piperidine derivative, which was converted to the dimethyl ester 63. The conditions used for the hydrogenation step kept the concomitant removal of the hydroxyl group to a minimum. The oxidation of alcohol 63 to the corresponding piperidone derivative 64 required careful control of the reaction conditions to avoid overoxidation to pyridine derivatives. This was accomplished by use of a polymeric carbodiimide in the Pfitzer-Moffat oxidation, which afforded the desired product 64 in 90% yield. For the introduction of the side chain, a new... 

Two new syntheses of racemic mesembrine have been described. In the first, outlined in Scheme 1, an improved synthesis of the penultimate 2-pyrroline (8) was achieved annelation of this afforded ( )-mesembrine (9). The second (Scheme 2) incorporates a regioselective borohydride imide reduction. Investigations on the biosynthesis of mesembrine alkaloids have revealed that a stereospecific protonation occurs at C-7 [see formula (9)] as one of the late stages. ... 

Total syntheses of racemic cassine (20), an alkaloid of the leaves of Cassia exdelsa Shrad., and of its 3-epimeride have been disclosed (Scheme 4). ... 

In this section, recent advances in the syntheses of racemic fluorinated amino acids and the related peptides that involve conceptually new synthetic designs are briefly summarized. 

Oxo-trans-l,2-cyclopentane dimethylcarboxylate is the starting material for two total syntheses of racemic Brefeldine A 236>>.238> (gq 121). 

Miscellaneous Antibiotics - Other primarily antibacterial antibiotics reported in 1978 are listed in Table Structural work was also published for the following previously reported compounds mlmosamycin (59) grlseorhodin C (60) ristomycin A,"" striatin A (61), ° Isochelocardin (62), pseudomonic acid A (63). and rlfamycln R.Marine sources have been used to obtain the new antimicrobial metabolites 64 and 65. Syntheses of racemic negamycin and its analogs were reported. ... 

This was followed by two other alternative syntheses of racemic horsfiline, one based on an oxidative rearrangement of the tetrahydro-y-carboline derivative 62 (Scheme 4) and another involving a spirocyclization between the 2-oxo-5-melhoxytryptamine derivative 63 and formaldehyde (Scheme S) [61]. 

White has also completed two syntheses of racemic methyl nonactate (154). The first approach controlled the C-8 alcohol stereochemistry, and the second provided a rapid entry into the ring system. The first sequence, outlined in Scheme 4.28, began with the opening of propylene oxide by 2-lithiofuran. The Friedel-Crafts acylation that followed also resulted in protection of the alcohol as the acetate to give 175 in 81% overall yield. Hydrogenation of the furan ring over rhodium on charcoal gave a 96% yield of tetrahydrofuran diastereomers... 

There have been several linear (as opposed to convergent) syntheses of racemic LTA4 methyl ester. All employ a sulfonium ylid at or near the last step to generate the epoxide by condensation with an aldehyde. It is conceivable that an optically active ylid would induce optical activity in the epoxide-forming... 

Several convergent syntheses of racemic LTA4 methyl ester have been reported. The first of these was by Gleason and co-workerswho developed a very short, efficient synthesis of the key intermediate ( )-trans-S6 (Scheme 3.23). Corey and co-workers also prepared the same racemic intermediate, albeit by a slightly longer route. Scheme 3.23 summarizes the synthesis of the various intermediates and Scheme 3.24 indicates the various isomers of ( )-LTA4 methyl ester obtained. The group at the Lilly Research Centre has examined... 

Scheme 3.24. Convergent syntheses of racemic LTA4 methyl ester and double-bond isomers.

So popular are the frog alkaloids as synthetic targets, and so numerous are the published approaches to them, that Takahata and Momose discussed only enantioselective syntheses in their survey in Volume 44 (2). In the interests of brevity, the ensuing discussion will perforce follow the same course. However, references to syntheses of racemic alkaloids published in the post-1986 period will be cited for completeness. In order to simplify the presentation, the syntheses are grouped according to the structural sub-class of the target alkaloids. 

Two short syntheses of racemic ipalbidine ( )-(842) are shown in Scheme 109. The synthesis by Jefford et al. commenced with conjugate addition between pyrrole and Ae atropate ester 849 followed by homologation of the acid 850 with diazomethane and rhodium-induced intramolecular carbene cyclization of the resulting diazoketone 851 (574). The bicyclic product 852 was converted into ( )-842 in a further four steps. The approach taken by Danishefsky and Vogel centered on acid-catalyzed cyclocondensation between the silyl ketene acetal 853 and A -pyrroline (854) to give indolizidinone 855 (575). Reduction of the lactam and cleavage of the aryl ether completed the synthesis of ( )-842. 

Two formal syntheses of racemic lasubines I and II are shown in Scheme 118. 

The procedure given here describes the preparation and use of N-(benzyloxycarbonyl)-L-serine p-lactone for the synthesis of a protected -substituted alanine, N - benzyloxycarbonyl)-P—(pyrazol-l-yl)-L-alanine. This compound occurs in watermelon seeds,9 and has been used as a histidine analog.Its synthesis illustrates how serine p-lactones can provide convenient access to other p-substituted alanines such as mimosine, willardiine, quisqualic acid, and stizolobic add which occur in higher plants.5a,io Many previous chemical syntheses of racemic pyrazolylalanine have been published the best of these routes appear to be from acetamidoacryiic acid (94-96% yield) and from 0-acetylserine (40-45%).The... 

Racemic methyloctalone 3 has been used as a starting material for many transformations as well as for syntheses of racemic natural compounds. In the following examples, the absolute configuration of the methyloctalone that would be required to obtain the natural enantiomer is indicated in parentheses p-g orgonene ... 

An important class of compounds that can be prepared by this route is the 2-arylpropionitriles, precursors for the widely used anti-inflammatory 2-arylpro-panoic acids [3]. Of these, only naproxen [( SJ-2-(6-methoxynaphthyl)propanoic acid] is sold as an optically pure drug. Nugent and McKinney first reported efficient syntheses of racemic ibuprofen and naproxen via the Ni[P(0-p-tolyl)3]4-catalyzed hydro cyanation of the corresponding vinylarene precursors (Scheme 2)... 

Two total syntheses of racemic bulnesol (349) have now been reported. In a consideration of the stereochemical features incorporated in the bicyclo[5,3,0]-... 

As noted previously (1), actinidine (14) was first synthesized by Sakan and colleagues (176) in racemic form. Interest in this area has continued, and several syntheses of racemic (134) and chiral actinidine (14) have appeared (177-183). 

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