Secoiridoids synthesis

Biosynthesis characterization chemistry classification iridoids pharmacology secoiridoids synthesis... 

Selective oxidation of a primary hydroxyl group. The first synthesis of the secoiridoid 4 has been achieved from the tetraacetate (1) of secologanin, the biological precursor of secoiridoids. Dihydroxylation of 1 with Os04 and potassium... 

A recent synthesis of the tricyclic secoiridoid ( )-sarracenin (98) relied on the Patemo-Biichi addition of acetaldehyde and cyclopentadiene as the initial step. Irradiation of cyclopentadiene and acetaldehyde provided a 5 1 mixture of bicyclic oxetanes (97) and (96) in 5-10% yield. Treatment of the crude photolysate with CSA and methanol followed by tosylation of the cmde product gave (99), which represents the toluenesulfonate ester derived from the major oxetane (97). The tosylate was displaced by the anion prepared from dimethyl 3-styrenylmalonate to afford the substituted malonate (100) in 84% yield (Scheme 10). Attempts to effect ring opening of the oxetane mixture were unsuccessful. Decarboxylation and demethylation gave the alcohol (102) which was subjected to ozonolysis and reductive work-up to afford ( )-sarracenin in 60% yield. The oxetane-based synthesis is noteworthy due to its brevity and use of a biosynthetically postulated trialdehyde equivalent. 

This last compound was selectively oxidised at the vicinal diol function with sodium periodate and successively with Jones s reagent, affording the desired acid 8. Direct esterification of compound 8 with dioxy-phenyl-ethanol 14, having phenolic functions protected with benzyl moieties, gave the key intermediate secoiridoid 9. The last step of the synthesis is the stereoselective reduction of 9 that afforded the alcohol 10... 

Two other non-glycosidic secoiridoids (see Figure 11) have been isolated from O. europaea. Compound 27 is the elenolic acid, described by Panizzi et al. [2], whereas compound 28 is its methyl ester whose total synthesis was accomplished by MacKellar et al [29], so demonstrating the absolute configuration of these two compounds. 

Allylic alcohol 846 has been employed in the synthesis of several natural products, as illustrated in Scheme 114 for the preparation of ( —)-elenolic acid (856), a secoiridoid monoterpene isolated from the olive Olea europea. The initial reaction is an orthoester Claisen rearrangement of 846 using triethyl orthoacetate, followed by lactonization with pyridinium / -toluenesulfonate. The resulting lactone is obtained as a 3 1 mixture of cw-850 and its trans isomer. After stereospecific alkylation of 850 with allyl bromide, the conversion of 851 to 852, which is essentially an expansion of the lactone by insertion of a methylene unit, requires five steps to accomplish. The remainder of the synthesis is uneventful, and furnishes pure 856 [234]. 

The reaction ofa chiral 5,7-dioxoperhydro-l,4-oxazepine withcyclopentene-l,2-dionedimer(21) in the presence of triethylamine in refluxing dichloromethane afforded one pure stereoisomer of the 2,1-trans Michael adduct in 60% yield <90TL20,90TL2033), which has been used as key intermediate for the asymmetric synthesis of virtually all monoterpenoid alkaloids and secoiridoids (Scheme 6)... 

The cleavage reaction was used for a synthesis of secoiridoids for example, secologanin aglycone O-methyl ether (6) was obtained by fragmentation of (5) in respectable yield. ... 

These chemical compounds are classified within the monoterpenoids, and are also known as secoiridoids. In the figure, the biosynthetic pathway from /-citronellal to sweroside, swertiamarin, and gentiopicroside is shown [9]. The study of the biosynthetic pathway was carried out using S.japon-ica or Gentiana triflora, and it was shown that gentiopicroside was derived from sweroside via swertiamarin. The structure elucidation, synthesis, and biosynthesis of the monoterpenoid alkaloids were reviewed by Cordell [10,11],... 

Contents L. Jaenicke and F.-J. Marner The Irones and Their Precursors. — M. Lounasmaa and P. Somersalo The Condylocarpine Group of Indole Alkaloids. — U. Sequin The Antibiotics of the Pluramycin Group (4//-Anthra [l,2- ]pyran Antibiotics). — R. M. Wenger Cyclosporine and Analogues — Isolation and Synthesis — Mechanism of Action and Structural Requirements for Pharmacological Activity. — H. Inouye and S. Uesato Biosynthesis of Iridoids and Secoiridoids. 

Tietze, L.-F. (1983) Secologanin, a biogenetic key compound - Synthesis and biogenesis of the iridoid and secoiridoid glycosides. Angew. Chem. Inti. Edn. Engl., 22,828-841. 

Iridoids are a large and stmcturally diverse class of secondary metabolites of monoterpenoid origin [10, 11]. Their sttuc-tural parent system is the iridane skeleton, which is derived from geraniol (6) by a cyclization pathway that is mechanistically different to the cyclization reactions that are usually found in classical terpene chemistry [1, 12], Further enzymatic transformations then give the fundamental iridoid skeleton or the thereof derived secoiridoid motive (with an alternative connectivity as shown in Scheme 6.10), which often serves as a building block for the synthesis of more complex monoterpenoid indole alkaloids [1]. Noteworthy, hereby the isoprene mle is often not fulfilled anymore as the terpenoid parts of such compounds sometimes contain nine carbon atoms only due to a decarboxylation step somewhere in the sequence. Very often iridoids and secoiridoids are present as glycosides in nature. 

Minfiensine, a secoiridoid indole alkaloid, was isolated from the African plant Strychnos minfiensis by Massiot and co-workers in 1989. The unique structure feature of the 1,2,3,4-tetrahydro-9a,4a-(iminoethano)-9//-carbazole has received much attention for the synthetic efforts and has culminated in several elegant total syntheses. For example. Overman et al. reported on the first and second total synthesis of (-l-)-minfiensine. " In addition, Qin et al. revealed a synthesis of ( )-minfiensine in 2008. Recently, MacMillan and co-workers reported on a nine-step enantiose-lective total synthesis of (-l-)-minfiensine via the key step reaction of organocatalytic Diels-Alder cyclization and amine heterocyclization cascade (Scheme 21.32). For the key step reaction in their approach, reaction of 2-vinylindole 139 and 3 equivalents of propynal in the presence of secondary amine catalyst 140 followed by the addition of NaBH4, stereoselective afforded the tricyclic alcohol 142 via a iminium activated endo-selectiye Diels-Alder cycloaddition and a 5-exo amine heterocy cliz ation. 

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