Tetrahydrofuran natural products

U. Nubbemeyer et al. achieved the enantioselective total synthesis of the bicyclic tetrahydrofuran natural product (+)-dihydrocanadensolide via a key step utilizing the diastereoseiective zwitterionic aza-Claisen rearrangement of an N-allylpyrrolidine. ... 

Brown, M. J., Harrison, T., Overman, L. E. General approach to halogenated tetrahydrofuran natural products from red algae of the genus Laurencia. Total synthesis of ( )-trans-kumausyne and demonstration of an asymmetric synthesis strategy. J. Am. Chem. Soc. 1991,113, 5378-5384. 

Moeller synthesized tetrahydrofuran natural products (+)-linalool oxide <01OL2685> and (+)-nemorensic acid <01TL7163> by employing intramolecular coupling reactions of enol ether radical cations as well as ketene dithioacetal radical cations with oxygen nucleophiles. 

Xiong used an acid-mediated epoxide-opening cascade to prepare a penta-tetrahydrofuran structure for the synthesis of the tetra-tetrahydrofuran natural product omaezakianol (152 Scheme 4.31) [66]. This allowed for the synthesis of cyclization precursor 153 from squalene. Exposing 153 to CSA provided pentacycle 154 in a 21% yield that includes the formation of the epoxides. Reductive opening resulted in... 

Given the relatively rare appearance of oxetanes in natural products, the more powerful functionality of the Patemo-Biichi reaction is the ability to set the relative stereochemistry of multiple centers by cracking or otherwise derivitizing the oxetane ring. Schreiber noted that Patemo—Btlchi reactions of furans with aldehydes followed by acidic hydrolysis generated product 37, tantamount to a threo selective Aldol reaction. This process is referred to as photochemical Aldolization . Schreiber uses this selectivity to establish the absolute stereochemistry of the fused tetrahydrofuran core 44 of the natural product asteltoxin. ... 

Tetrahydropyran- and tetrahydrofuran-substituted rings are common in many complex natural products, such as polyether antibiotics, displaying a wide range of biological properties [4]. An appropriate combination of OH-directed diastereose-lective epoxidation of y- and 8-alkenols [VO(acac)2/TBHP or MCPBA] [5] or ster-... 

Tetrahydrofurans 53 should be of synthetic interest because of the many natural products containing a bicyclic tetrahydrofuranoid skeleton or structural element [30]. The double bond would allow further synthetic transformations. While the chances of a regioselective isomerization of 46 to the allyl aminosulfoxonium salts 52 seemed to be good, the prospects of a cyclization of the latter with formation of 53 were considered to be less promising because of the poor nucleophilicity of the silyloxy group. 

Viewed (and drawn) in a terpene-like perspective, C-glycosyl compounds are in fact functionalized tetrahydrofurans and tetrahydropyrans. As such, they can be considered as versatile chirons for the synthesis of a variety of natural products containing cyclic ether motifs, such as in the ionophores. 

The popular approach to tetrahydrofurans involves an electrophilic process and the commonly used electrophiles for the cyclization are acids, oxygen, halogen, mercury (see Section 3.11.2.2.9) and selenium. The ionic hydrogenation of furans with excess triethyl-silane in trifluoroacetic acid affords high yields, e.g. 2-methylfuran is reduced to 2-methyl-tetrahydrofuran and 2-ethylfuran to 2-ethyltetrahydrofuran (see Section 3.11.2.5). The synthesis of several dihydro and tetrahydrofurans containing natural products by chirality transfer from carbohydrates has been used successfully for total synthesis, e.g. (-)-nonactic acid. A reasonable yield of 2-alkyltetrahydrofuran was prepared from 4-alkylbut-l-en-4-ol by hydroboration followed by cyclization with p-toluenesulfonic acid. 

Tetr 39 2323 (1983) (Recent Advances in the Preparation and Synthetic Applications of Oxiranes) 43 3309 (1987) (Synthetic Routes to Tetrahydrofuran, Tetrahydropyran, and Spiroketal Units of Polyether Antibiodcs and a Survey of Spiroketals of Other Natural Products) SO 8885 (1994) (Chemical and Biological Synthesis of Chiral Epoxides)... 

An equimolar mixture of 3,4,5-trimethoxy phenyl iodide 157, lithium propargyl alkoxide 158, and diethyl ethoxymethylene malonate 159 was stirred at room temperature in the presence of a palladium catalyst. Then, to the resulting intermediate 161 potassium t-butoxide was added, and the ensuing base-promoted decarboxylative aromatization afforded tetrahydrofuran MCR adduct 162 in good yield. The ester was first reduced and the furan ring was hydrogenated with Raney nickel to furnish a diastereomeric mixture of products 163 in high yield. Further synthetic manipulations then provided a known precursor to the natural product. 

More recently, the formal total syntheses of some bioactive natural products bearing a tetrahydrofurane moiety were achieved by enzymatic Baeyer-Villiger oxidation using cyclopentanone monooxygenases (CPMOs) from Comamonas sp. 

Mihovilovic MD, Bianchi DA et al (2006) Accessing tetrahydrofuran-based natural products by microbial Baeyer-Villiger biooxidation. Chem Commun 42 3214—3216... 

Removal of the tri-wo-propylsilyl (TIPS) and tm-butyldimethylsilyl (TBS) protecting groups could be accomplished concomitantly with TBAF in tetrahydrofuran at 0 °C, but here competing elimination of the secondary bromide was observed. Better overall yields and cleaner conversion was observed when TBS ether was cleaved with 5 % aqueous HF in acetonitrile at 0 °C followed by removal of the acetylenic TIPS with TBAF under milder conditions of -78 °C.10 The diastereomers are not separated before the desilylation process therefore even a 3 1 mixture of E- and Z-enyne is obtained. Prelaureatin 4 and its F-isomer 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the alkyne is introduced via a Sonogashira reaction. 

Scheme 5. Natural products derived from oligoepoxides of the key building block squalene (as highlighted). Elegant total synthesis of the pentakis tetrahydrofuran system 26 by Xiong and Corey.

Co(modp)2 338a, oxygen, terf-butyl hydroperoxide, and isopropanol to 2-hydroxymethyltetrahydrofurans 419 in 53-79% yield with exclusive trans-selectivity [442]. Reduced tetrahydrofurans 420 were isolated as a side product. This method was applied in total syntheses of annonaceous acetogenins [443], such as gigantetrocin A [444, 445], asimilobin [446, 447], mucocin [448, 449], or bullatacin [450], as well as of the algal natural product aplysiallene [451]. 

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