Total synthesis of the formamicin aglycon,formamicinone

[structure: see text] The total synthesis of formamicinone (2), the aglycone of formamicin (1), has been accomplished via the late-stage Suzuki cross-coupling of fragments 5 and 6, the macrolactonization of seco ester 14, and the Mukaiyama aldol reaction of aldehyde 3 and methyl ketone 4. An efficient and highly stereoselective second generation synthesis of vinyl iodide 6 is also described.     

Total synthesis of dehydroaltenusin

First total synthesis of dehydroaltenusin, a natural enzyme inhibitor, is described. The key step involves Suzuki-couplig reaction of aryl triflate prepared from 2,4,6-trihydroxy benzoic acid with a catechol-derived boronic acid. The synthetic sample was evaluated as a potent inhibitor against an eukaryotic DNA polymerase α.     

Total synthesis of gambierol

The convergent total synthesis of gambierol (1) is described. The octacyclic ether framework of 1 was constructed via the intramolecular allylation of alpha-chloroacetoxy ether followed by ring-closing metathesis. A modified Stille coupling was successfully applied to the synthesis of the triene side chain.     

Total synthesis of pyridovericin

The total synthesis of the naturally occurring kinase inhibitor pyridovericin 1 is reported. A flexible and efficient synthesis has been accomplished in good yield from readily available 2,4-dihydroxypyridine. Pyridovericin is a key intermediate in our proposed biomimetic synthesis of pyridomacrolidin 2.     

Total synthesis of capreomycin

Total syntheses have been achieved of capreomycin IA and IB according to our newly proposed structures. The β-lysine residue in the branch was introduced to the cyclic peptide moiety which was prepared by cyclization of the corresponding pentapeptide. Deprotection followed by conversion of β,β-diethoxyalanine residue to β-ureidodehydroalanine residue afforded the desired products, which were identical with natural capreomycins in all respects.     

Total synthesis of colletodiol

Colletodiol and 6-epi-colletodiol were synthesized from (5S,2E)-5-tetrahydropyranyloxy-2-hexenoic acid and p-toluenesulfonylethyl (4R,5R,7R,2E)-7-hydroxy-4,5-dimethylmethylenedioxy-2-octenoate.     

Total synthesis of Monatin

The naturally occurring sweetener Monatin, a diastereomer of Monatin, and a phenyl analogue of Monatin have been prepared and isolated in their enantiomerically pure forms.     

Total synthesis of spicamycin

The first total synthesis of one of the spicamycin congeners, SPM VIII (3), is described. A preliminary model study for construction of the characteristic N-glycoside linkage in spicamycin using tetra-O-benzyl-beta-D-mannopyranosylamine (13) and halopurines 5 revealed that Pd-catalyzed conditions successfully provided the coupling products 14 and 15 in good yields. It was also shown that thermal anomerization of the N-glycosides easily occurred, which resulted in the predominant formation of the beta-anomer as the thermodynamically favored compound, and the activation energy of anomerization of 15 was estimated to be ca. 30 kcal/mol. The novel aminoheptose unit of spicamycin 6 was prepared stereoselectively by carbon elongation of an acyclic aldehyde, prepared by ring cleavage reaction of a highly functionalized cyclohexane derived from naturally abundant myo-inositol. The Pd-catalyzed coupling reaction of the beta-heptopyranosylamine 6 with protected 6-chloropurine 5d, followed by deprotection, provided spicamycin amino nucleoside 2, whose condensation with dodecanoylglycine completed the total synthesis of 3. This study confirmed the proposed unique structure of a novel nucleoside antibiotic.     

Total synthesis of hyptolide

The total synthesis of hyptolide, a naturally occurring α,β-unsaturated six-membered δ-lactone substituted with a polyoxygenated chain, is described. Sharpless kinetic resolution and opening of two different epoxy alcohols under two different conditions—Swern oxidation conditions and a radical reaction using Cp₂TiCl—fixed the stereocenters at C-9, C-11, and C-12, respectively. Brown’s asymmetric allylation reaction installed the remaining stereocenter at C-6. A RCM protocol was used for construction of the α,β-unsaturated six-membered δ-lactone moiety of the molecule.     

Total synthesis of heliophenanthrone

The total synthesis of rac-heliophenanthrone (3a) was achieved by a convergent approach, making use of a transition-metal-catalyzed domino process with an intramolecular Diels-Alder reaction at an isobenzopyrylium cation as key step.     

Total synthesis of isokidamycin

The synthesis of isokidamycin, which represents the first total synthesis of a bis-C-aryl glycoside natural product in the pluramycin family, has been completed. The synthesis features the use of a silicon tether as a disposable regiocontrol element in an intramolecular Diels-Alder reaction between a substituted naphthyne and a glycosyl furan and a subsequent O→C-glycoside rearrangement.     

Total synthesis of pentosidine

Pentosidine, a biologically important advanced glycation endproduct, has been accessed in a rapid, high-yielding manner. The synthesis was accomplished via a six-step sequence starting with 3-amino-2-chloropyridine and features a palladium-catalyzed tandem cross-coupling/cyclization to construct the imidazo[4,5-b]pyridine core.     

Total synthesis of agelagalastatin

The total synthesis of agelagalastatin, an antineoplastic glycosphingolipid, has been achieved. The synthesis involved an alpha-selective glycosylation of the ceramide moiety with the trisaccharide fluoride. The trisaccharide component was constructed employing the CB glycoside method which permitted a completely alpha-stereoselective galactofuranosylation.     

Total synthesis of psorospermin

The xanthone natural product psorospermin was synthesized in 13 steps with an overall yield of 1.7%. This compound shows potent antineoplastic activity in a variety of cancer cell lines.     

Total synthesis of clavulones

Total synthesis of clavulones in naturally occurring form has been accomplished by the aldol coupling of the hydroxy-cyclopentenone $\text{2}$ efficiently obtainable from 1,2-bis-trimethylsilyloxycyclopentene ($\text{4}$) by using 1,3-hydroxy transposition via the allylic methanesulfonate $\text{11}$ and the α,β-unsaturated aldehyde $\text{3}$.     

Total synthesis of prolycopene

A total synthesis of the tetra-Z-isomer (1, ‘prolycopene’) of lycopene found in fruits of the Tangerine tomatoLycopersicon esculentum, based on: (i) elaboration of the2Z, 6E-carbinol (4) from a Pd-coupling reaction between the vinyl bromide (2) and the Z-enynol(3) (ii) successive Wittig reactions between (6) and (7), [leading to (8)] and between (8) and (6), and (iii) partial catalytic hydrogenation of thebis-acetylene (9), is described.     

Total synthesis of ulithiacyclamide

The total synthesis of ulithiacyclamide ($\text{4}$) by twofold ring closure reaction of the bifunctional pentafluorophenyl ester $\text{2}$ is described.