First total synthesis of natural

In a study which was conducted simultaneously to the work in the Mehta group and which also aimed to prove the absolute configuration of natural kelsoene (1), Schulz et al. used a stereoselective approach starting from the enantiomerically pure chiral pool material (i )-pulegone 17 [9, 10] (see above). The final steps of their synthesis of the unnatural enantiomer of kelsoene (ent-l) were similar to the above-described first total synthesis of natural kelsoene (1) (Scheme 8). Taking into account the steric limitations of the system as communicated by Srinivas and Mehta, diquinane enone ent-6... 

In this account, we describe three first total synthesis of natural products, (+)-secosyrins 1 and 2, (-)-ichthyothereol," and ( )-8(3-hydroxystreptazolone by making the most of the significant features of the alkyne-Co2(CO)6 complexes 1 [propargyl cation stabilizing ability (Nicholas reaction), formal [2+2+1] cycloaddition (Pauson-Khand reaction), and their inherent steric bulkiness). 

Snider published the synthesis of desmethylamino FR901483 in 1998 [9] and one year later, the first total synthesis of natural (-)-FR901483 [2]. The disconnective analysis is outlined in Scheme 5. The key step in the retrosynthetic analysis is the disassembly of the azatricyclic structure of 1 by a retro-aldol process, which leads to aldehyde 6. In the forward sense, while this approach should provide efficient access to the ring system,... 

Many distinguished synthetic groups have carried out the total synthesis toward Maoecrystal V due to the complexity of the structure and the importance of its bioactivity. The thesis mainly focuses on two aspects the first part is the stereoselective construction of the tetracychc model system and the second part is the first total synthesis of natural product Maoecrystal V. Based on the model study, the total synthesis of Maoecrystal V is accomplished in 17 steps, 1.2% yield. 

Novel p-keto phosphonates (187) and (188) have been utilized by Zard et al. as radieal preeursors in addition reaetions to alkenes (Scheme 64) " and as substrates in a Horner-Wittig reaction with aldehydes and ketones (Scheme 65). The phosphonate precursor (187) was employed in the first total synthesis of naturally occurring pyridine alkaloids-xestamines C, E, and H, " while the precursor (188) was utilized in the one-pot synthesis of variously functionalized thieno[2,3-b]thiopyran-4-ones (189) (Scheme 65). ... 

In 1975, Pattenden etal. reported the first regiospecific synthesis of permethylated pulvinic acids 46 [48] and pulvinones 45 [49] by condensation of 44 with aroyl formates and aryl aldehydes, respectively, followed by dehydration (Scheme 1.5). Interestingly, Pattenden s pioneering work allowed the first total synthesis of naturally occurring pulvinones, first isolated from natural sources in 1973 [3b] but... 

The older approaches to the penam skeleton from acyclic precursors were based on the azetidinone ring formation by [2+2] cydoaddition of ketens or enolates to imines and by cyclization of fS-amino add precursors. These methods have been reviewed by Jastrzebski and Van Koten [76] and by Marchand-Brynaert and Brule [77]. Sheehan and Henery-Logan [78] developed the first total synthesis of natural penicillin in 1957. Baldwin and coworkers [79] reported the first highly stereocontrolled total synthesis of natural penicillin. Most of the recent methods for the synthesis of nonnatural penams, however, employ 2-azetidinones with appropriate functionalities for fused ring cyclization. 

In the first of them, the ascending" type of synthesis with the subsequent addition of rings C and D to the initial AB fragment is considered. In this section, the syntheses of equilenin by Bachmann (Scheme 2) and Johnson (Scheme 4), which have not lost their importance, and also the synthesis of an isomer of estrone by Bachmann (Scheme 11), the first total synthesis of natural estrone by Anner and Miescher (Scheme 12), and the synthesis of 19-norpregnanes by Nagata (Scheme 13) are of interest. 

We reported the first total synthesis of naturally occurring 1 in 2006 [8,9]. Our retrosynthetic plan is outlined in Scheme 4. We envisioned that target molecule... 

In 2010, we achieved the first total synthesis of naturally occurring 2 [9]. Our synthetic plan is outlined in Scheme 8. The y-pyrone moiety present in 1 is considered to be an equivalent to vinylogous methyl ester therefore, the hydrolysis of this moiety followed by spmitaneous tautomerization to a-pyrone would form 2 via the plausible intermediates 34 and 35. To the best of our knowledge, the method for the conversion of 1 to 2 was hitherto unknown hence, this approach posed a cmisiderable challenge from the synthetic viewpoint. 

Caruso, T. and Spinella, A. (2002) First total synthesis of natural aplyolides C and E, ichihyotoxic macrolides isolated fi-om the skin of the marine mollusc Aplysia depdans. Tetrahedron Asymmetry, 13, 2071-2073. 

Many notable examples of the synthesis of complex natural products from optically pure starting materials have been reported (70). One synthesis of considerable interest is that of taxol [33069-62-4] (74), a potent antitumor agent used clinically. The starting material (73) used ia the first total synthesis of taxol is produced ia enantiomericaHy pure form from inexpensive and readily available /-camphor [464-48-2] (72) (73). 

In 1952, it was reported that a constituent of excretions from female American cockroaches of the species Periplaneta ameri-cana is an extraordinarily potent sex pheromone.1 Early attempts to isolate and characterize the active compounds were hampered because individual cockroaches store only minute amounts of the pheromone ( 1 pg), and a full 25 years elapsed before Persoons et al. reported the isolation of two extremely active compounds, periplanones A and B.2 The latter substance is present in larger relative measure and its germacranoid structure (1, without stereochemistry) was tentatively assigned on the basis of spectroscopic data. Thus, in 1976, the constitution of periplanone B was known but there remained a stereochemical problem of a rather serious nature. Roughly three years intervened between the report of the gross structure of periplanone B and the first total synthesis of this substance by W. C. Still at Columbia.3... 

Nakadomarin A ((-)-145) is a marine natural product with a unique hexa-cyclic structure (Scheme 26). Recently, the first total synthesis of its enantiomer... 

Migrastatin (192) (Scheme 37) is a novel macrolide natural product that displays an inhibitory effect on the migration of human tumor cells. After an RCM-based synthesis of the 14-membered macrolide core of 192 [94], Danishefsky also achieved the first total synthesis of the natural compound [95], using the fully functionalized tetraene 191 as the metathesis precursor. Under the conditions shown in Scheme 37, the ring-closing step proceeded (E)-selectively with exclusive participation of the two terminal double bonds in 191, delivering only the ( , ,Z)-trienyl arrangement present in 192. 

In 1995, these authors applied this methodology to the first total synthesis of the biosynthetically and unusual marine natural products, gracilins B and Thus, the key step of this synthesis was the enantioselective Diels-Alder reaction of 2-((trimethylsilyl)methyl)-butadiene with A-(2-iert-butylphenyl)maleimide in... 

Another effective combination of two radical cyclization steps has been demonstrated by Sha and coworkers during the course of the first total synthesis of (+)-paniculatine (3-24), a natural alkaloid belonging to the subclass of Lycopodium alkaloids [13]. 3-24 has a unique tetracyclic scaffold with seven stereogenic centers [14]. Although no special features of (+)-paniculatine have so far been documented, other Lycopodium alkaloids are reported to be potent acetylcholinesterase inhibitors, or show promising results in the treatment of Alzheimer s disease [15]. When... 

The key feature of the first total synthesis of (+)-homopumiliotoxin 223G 418 was a Lewis acid-induced, chelation-controlled propargylation of the trifluoroacetate salt of (. )-2-acetyl pi peri dine 415, derived from iV-Cbz-L-pipecolinic acid. Alkyne 416 thus formed was transformed after several steps into 417, which was cyclized by activation of the primary hydroxyl with the carbon tetrabromide-triphenylphosphine system to give the natural product (Scheme 98) <1998TL2149>. 

Deprotection followed by A -acylation of 40 gave highly advanced diene 41 which was subjected to the final RCM with 42 and the desired dilactam (-)-(24Z)-43 was isolated from the mixture of geometrical isomers ZIE = ca. 2 3). Reduction of 43 with Red-Al resulted in the first total synthesis of enr-(+)-nakadomarin A from the readily available chiral acid 22. The absolute configuration of natural nakadomarin A was assigned to be R (Scheme 10.4) [9]. 

In 1978 Oppolzer and Petrzilka reported the first enantioselective total synthesis of natural (+)-luciduline from (i )-5-methyl-2-cyclohexenone (31) by a sequence of seven steps in 33% overall yield [9]. 

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