Total synthesis, structure revision, and absolute configuration of (-)-brevenal

Total synthesis of structure 1 originally proposed for brevenal, a nontoxic polycyclic ether natural product isolated from the Florida red tide dinoflagellate, Karenia brevis, was accomplished. The key features of the synthesis involved (i) convergent assembly of the pentacyclic polyether skeleton based on our developed Suzuki-Miyaura coupling chemistry and (ii) stereoselective construction of the multi-substituted (E,E)-dienal side chain by using copper(I) thiophen-2-carboxylate (CuTC)-promoted modified Stille coupling. The disparity of NMR spectra between the synthetic material and the natural product required a revision of the proposed structure. Detailed spectroscopic comparison of synthetic 1 with natural brevenal, coupled with the postulated biosynthetic pathway for marine polyether natural products, suggested that the natural product was most likely represented by 2, the C26 epimer of the proposed structure 1. The revised structure was finally validated by completing the first total synthesis of (-)-2, which also unambiguously established the absolute configuration of the natural product.     

A concise synthesis of (+)-SCH 351448

[structure: see text] We describe a highly convergent synthetic approach to the natural product (+)-SCH 351448 (1)-a hexane-soluble heptacoordinate monosodium salt of a C(2)-symmetrical macrocyclic dilactone. Our approach implements a photochemical acylation as the key step to combine two nearly identical but orthogonal C1-C29 fragments, followed by a base-induced intramolecular acylation and deprotection to yield the natural product.     

Diastereoselective one-pot Wittig olefination-Michael addition and olefin cross metathesis strategy for total synthesis of cytotoxic natural product (+)-varitriol and its higher analogues

A stereoselective route for the total synthesis of anticancer marine natural product (+)-varitriol (1) is detailed herein. The impressive biological activity and interesting structural features of natural (+)-varitriol fuelled us to undertake the synthesis of some higher analogues (1a-j) of this molecule. The key features of the synthetic strategy include one-pot Wittig olefination followed by a highly diastereoselective oxa-Michael addition to assemble stereochemically pure tetrasubstituted THF moiety of the natural varitriol and olefin cross metathesis to couple the aromatic part with tetrasubstituted THF moiety. The total synthesis of title natural product is efficient with 21.8% overall yield for 9 linear steps from D-ribose and thus facilitates the more scaled-up practical route for the synthesis of 1 and its analogues as well. The synthetic (+)-varitriol (1) and its analogues were screened for their cytotoxicity. The present synthetic approach paves the way for preparation of numerous analogues of the title natural product for drug development.     

Total synthesis of trans,trans-Sanguinamide B and conformational isomers

The first total synthesis of Sanguinamide B is reported, prepared via an efficient synthetic strategy. The natural product, trans,trans-Sanguinamide B (1), was generated in a thermodynamic ratio with trans,cis-Sanguinamide B (2) and cis,cis-Sanguinamide B (3). Complete conversion of the cis,cis-Sanguinamide B conformer (3) to the natural product (1) and the trans,cis- conformer (2) was achieved by heating to 170 °C. Biological evaluation indicated that the Sanguinamide B conformers disrupted the activity of a virulence determinant in P. aeruginosa.     

Total Synthesis of the Natural Product-Pinosylvin and its Analog

Polyhydroxy stilbenes were proved to have many biological activitiesl'2. 'We havereported the total synthesis of tWo natural products-resveratrol (3,5,4'-tTihydroxylstilbene) and isorhapontigenin 3'4 which were first found in a traditional Chinese herb,G.Parvghlium by M. Lins et al. Herein,we want to present the total synthesis of anothernatural hydroxyl stilbene, pinosylvin (3,5-dihydroxy stilbene,10) isolated from this plantand its analog (3,5,3',5'-tetfahydroxy stilbene,9 ). In the synth…     

Total synthesis, structure revision, and absolute configuration of (+)-yatakemycin

The total synthesis of the reported structure 2 for yatakemycin, an exceptionally potent, naturally occurring antitumor agent disclosed in 2003, and its lack of correlation with the natural product are detailed. On the basis of spectroscopic distinctions between 2 and yatakemycin, the natural product structure was reformulated as 3, now bearing a thiomethyl ester versus thioacetate in the left-hand subunit. Total synthesis of 3 provided a compound nearly identical to but still subtly distinct from the natural product. A second reformulation of the yatakemycin structure as 1, incorporating the alternatively substituted right-hand subunit as well as the initial thiomethyl ester reformulation, was confirmed by total synthesis of both (+)- and ent-(-)-1 in studies that also unambiguously established the absolute configuration of the natural product.     

Synthesis of the enantiomer of the structure assigned to the natural product nobilisitine A

The synthesis of the enantiomer of the structure, 1, assigned to the natural product nobilisitine A has been accomplished using the enantiomerically pure cis-1,2-dihydrocatechol 4 as starting material. The (1)H and (13)C NMR spectral data derived from compound ent-1 do not match those reported for the natural product, thus suggesting its structure has been incorrectly assigned.     

An Improved Synthesis of the Natural Product Isorhapontigenin

lsorhapontigenin (I ) is a natural product with many biological activities. M. Linel a/ first isolated it from the traditional Chinese herb, G.parvdoliunl 1. The totalsynthesis of (I ) has been reported' using miting reaction and TMS as the protectinggroup. the reaction gives both E and Z-stilbene, In an attempt to obtain enough sample of(I ) for screening its bioactivities, we have developed an alternative synthetic route toprepare isorhapontigenin through a 7 steps reaction sequence 3. H…     

3-氧-11,12,13-三羟基桉烷-4-烯的简便全合成

报道了一种全合成3-氧-11,12,13-三羟基桉烷-4-烯(1)的简便方法. 对于该化合物及其衍生物的药理活性研究目前正在进行中.     

Synthesis of terpene and steroid dimers and trimers having cyclobutadienyl-Co and aromatic tethers

The reaction of natural product derived propargylic alcohols with CpCo(CO)2 produces three new types of natural product hybrids having two or three terpene or steroid fragments. The tether joining the natural product subunits is built during the reaction. Type 1 hybrids have two terpene or steroid moieties joined by a CpCo-cyclobutadiene tether, with the two units disposed in a 1,2-arrangement (9, 14, 22). Type 2 hybrids have a Co-cyclopentadienone tether (10). Type 3 has three units of terpene or steroid joined to a benzene ring (11, 12, 15). An unusual Co-mediated beta-carbon elimination pathway of propargylic alcohols leading to ketones (an unknown process in this chemistry) has been observed.     

Total synthesis of (-)- and (+)-dysibetaine

Glycidamides 6R and 6S were elaborated to (R,R)- and (S,S)-dysibetaines (1R and 1S) by intramolecular alkylation and functional group modification in 23% overall yield. The absolute stereochemistry of natural dysibetaine was established as S,S by comparison of the optical rotation of the natural product with that of the synthetic materials.     

Total synthesis of (±)-spiniferin-1 via a polyfluoroalkanosulfonyl fluoride induced homoallylic carbocation rearrangement reaction

A facile total synthesis of marine natural product (±)-spiniferin-1 has been accomplished in eight steps with 28.9% overall yield, involving a rearrangement reaction initiated by polyfluoroalkanosulfonyl fluoride to construct the 1,6-methano[10]annulene core of the natural product as a key step.     

Solid-phase synthesis and configurational reassigment of callipeltin E. Implications for the structures of callipeltins A and B

Two possible isomers of the natural product callipeltin E (1, 5) were synthesized by using an Fmoc-based solid-phase strategy in 7 steps, in 20% and 26% overall yields, respectively. The (1)H NMR spectrum of synthetic 5 correlated closely with that of the natural product, whereas that of 1 did not, providing confirmation of the configurational reassignment of the N-terminal residue of callipeltin E as D-allothreonine. This result strongly implies that the corresponding residue in the closely related cyclic depsipeptides callipeltins A and B should also be considered a D-allothreonine residue.     

Pyrolysis of polyisoprenes. I. Differentiation between natural and synthetic cis-1,4-polyisoprenes

Two methods of differentiating between natural rubber and synthetic cis-1,4-polyisoprenes have been examined. Both techniques depend on the presence of Ziegler-Natta catalyst residues in the synthetic polymers. The major pyrolysis product of cis-1,4-polyisoprenes at 350°C is 1-methyl-4-(1-methylethenyl)cyclohexene. This can undergo disproportionation to yield 1-methyl-4-(1-methylethyl)benzene and methyl-(1-methylethyl)cyclohexenes. It is this disproportionation reaction, catalyzed by Ziegler-Natta catalyst residues or by carbon black, that is responsible for the different product ratios obtained on pyrolysis of natural rubber and Ziegler-Natta catalyzed cis-1,4-polyisoprenes. Lithium alkyl-polymerized polyisoprenes undergo this secondary disproportionation reaction only in the presence of carbon black. Derivative thermogravimetric traces of black-filled sulfur vulcanizates of natural rubber and synthetic polyisoprenes are significantly different because polymerization catalyst residues promote cyclization of the polymer.     

Total synthesis of natural (levo) and enantiomeric (dextro) forms of prostaglandin El

1 newly-discovered method of synthesizing PGE1 (prostaglandin E1) is explained and diagrammed chemically. Recrystallization of the synthetic product produced material identical in all respects with natural PGE1. The synthetic product showed the same infrared spectrum and chromatographic values as racemic and natural forms of PGE1. The biological activity of the synthetic product was found to be .1% of that of the naturally-occurring PGE1 in the stimulation of smooth muscle contraction. This is the 1st report of a total synthesis of PGE1. Research continues on improvements in this synthesizing method and on discovering other synthetic approaches to PGs.     

Stereodivergent Synthesis and Stereochemical Reassignment of the C79–C104 Fragment of Symbiodinolide

We have synthesized eight possible diastereoisomers 3 a – h of the C79–C97 fragment of symbiodinolide ( 1 ) in a stereodivergent manner by utilizing a dithiane addition to the aldehyde as a key step. Comparison of the ¹³C NMR chemical shifts of the natural product 1 and the synthetic products 3 a – h indicated that the relative stereostructure of this fragment in symbiodinolide ( 1 ) is that represented in 3 a or f . We have stereodivergently synthesized eight possible diastereoisomers of the C94–C104 fragment 4 a – h , and we have compared their ¹³C NMR chemical shifts with those of the natural product, which established the relative stereochemistry of this fragment to be that described in diastereoisomers 4 a or e . By combining the stereostructural outcomes of the C79–C97 and C94–C104 fragments, we have proposed four candidate compounds of the C79–C104 fragment 2 a – d . We also synthesized diastereoisomers 2 a and b ( 2 a in the preceding article; Chem. Eur. J. 2015 , DOI: 10.1002/chem.201503880) by a Julia–Kocienski olefination and diastereoisomers 2 c and d by a Wittig reaction. By comparing the ¹³C NMR chemical shifts of natural symbiodinolide ( 1 ) with those of the synthetic products 2 a – d , we have reassigned the stereostructure of the C79–C104 fragment of natural product 1 to be that depicted in diastereoisomer 2 b .     

Tandem Rh(i)-catalyzed [(5+2)+1] cycloaddition/aldol reaction for the construction of linear triquinane skeleton: total syntheses of (+/-)-hirsutene and (+/-)-1-desoxyhypnophilin

A tandem reaction involving a Rh(I)-catalyzed two-component [(5+2)+1] cycloaddition and an aldol condensation has been developed to construct the tricyclo[6.3.0.02,6]undecane skeleton and its heteroatom-imbedded analogues. Meanwhile, this method has been successfully applied to natural product synthesis for the first time. The present strategy enables a straightforward approach to the natural linear triquinane skeleton, as demonstrated by concise and step economical syntheses of hirsutene and 1-desoxy-hypnophilin, whereby the linear triquinane core is diastereoselectively established in one manipulation with correct placement of all stereocenters, including two quarternary centers. This first application of the Rh(I)-catalyzed [(5+2)+1] cycloaddition in natural product synthesis highlights the efficiency of this methodology for constructing complex fused ring systems.     

Synthesis of (+/-)-hamigeran B, (-)-hamigeran B, and (+/-)-1-epi-hamigeran B: use of bulky silyl groups to protect a benzylic carbon-oxygen bond from hydrogenolysis

Enone 42 was converted into diene 56, which was then subjected to hydrogenation. Use of the tert-butyldimethylsiloxy groups enforces facial selectivity and protects the C(5) oxygen from hydrogenolysis. The resulting product (55) is easily converted into hamigeran B (1), a marine natural product with powerful activity against herpes and polio viruses. Optically pure enone 73 was made by use of a Meyers' auxiliary and converted into (-)-hamigeran B with the natural absolute configuration.     

Generation of two new macrolactones through sequential biotransformation of dihydroresorcylide

Biotransformation is an effective method to generate new derivatives from natural products. Combination of various enzymes or whole-cell biocatalysts creates new opportunities for natural product biosynthesis. Dihydroresorcylide (1) is a phytotoxic macrolactone from Acremonium aeae. It was first chlorinated at C-11 by an engineered Escherichia coli BL21-CodonPlus (DE3)-RIL/pJZ54 strain that overexpresses a fungal flavin-dependent halogenase, and subsequently glycosylated at 12-OH by Beauveria bassiana ATCC 7159, giving rise to a novel derivative, 11-chloro-4'-O-methyl-12-O-beta-D-glucosyl-dihydroresorcylide (3). Although 1 can be converted into a new 4'-O-methyl-glucosylated derivative 4 by B. bassiana, this product cannot be further chlorinated by E. coli BL21-CodonPlus (DE3)-RIL/pJZ54 to afford 3. The sequence of these two biotransformation steps was thus restricted and not interchangeable. This sequential biotransformation approach can be applied to other structurally similar natural products to create novel derivatives.