Complex aldol reactions for the construction of dense polyol stereoarrays: synthesis of the C33-C36 region of aflastatin A

[reaction: see text]. Facial selectivity in the addition of boron enolates of alpha-oxygenated ketones to anti-disposed alpha,beta-bisalkoxy aldehydes is controlled by the aldehyde vicinal diol protecting group. Protection of the diol as an acetonide results in the exclusive formation of the anti-syn-anti stereoarray found in the C(33)-C(36) region of aflastatin A.     

A [Pd]-mediated ω-alkynone cycloisomerization approach for the central tetrahydropyran unit and the synthesis of C(31)-C(48) fragment of aflastatin A

A concise assembly of the central tetrahydropyran unit of aflastatin A featuring a Pd-mediated alkynone cycloisomerization to provide a glycal and its subsequent stereoselective hydroboration to deliver the requisite stereochemistry at C(33) and C(34) centers is documented.     

Synthesis and confirmation of the absolute stereochemistry of the (-)-aflastatin A C9-C27 degradation polyol

[reaction: see text]. The C(8)-C(18) ethyl ketone and C(19)-C(28) aldehyde aflastatin A fragments were synthesized and coupled using a diastereoselective anti aldol reaction. This adduct was successfully converted into the C(9)-C(27) polyol degradation product of (-)-aflastatin A to confirm the relative and absolute stereochemistry of this region of the natural product.     

Highly stereoselective synthesis of vicinal diols by stannous chloride-mediated addition of hydroxyallylic stannanes to aldehydes

A new protocol for the synthesis of vicinal diols was accomplished by the reaction of unprotected α-hydroxymethylmetals, as hydroxymethyl anion equivalents, with aldehydes. The treatment of hydroxyallylic stannanes, which were prepared from α,β-unsaturated aldehydes and Bu₃SnLi in situ, with various aldehydes gave but-3-en-1,2-diols in the presence of SnCl₂. The stereochemistry of the diol and olefin moieties demonstrated syn- and E-selectivities, respectively. We propose the following reaction mechanism; transmetalation of a hydroxyallylic stannane with SnCl₂ gives a rearranged allylic tin(II) species that undergoes aldehyde addition via a cyclic transition state. The strict interaction between the unprotected hydroxy moiety and the tin(II) center accounts for the selectivity.     

Studies in sesquiterpenes—XLIX: Sesquiterpenes from Ferula jaeschkeana vatke (part 1): jaeschkeanadiol—structure,stereochemistry

A new sesquiterpene diol, now named jaeschkeanadiol, has been isolated from the roots of Ferula jaeschkeana Vatke and is shown to possess structure1. Its stereochemistry has been established by a direct chemical correlation with laserol (9).     

Short synthesis of epi-cytoxazone via oxazoline formation through intramolecular benzylic substitution of a bis-trichloroacetimidate

A short and efficient method for synthesizing epi-cytoxazone via the corresponding oxazoline intermediate was developed. The formation of the oxazoline ring, which proceeds through an S_N1 mechanism to ensure that the trans-oxazoline stereochemistry is retained, was induced by intramolecular benzylic substitution of a 1,2-bis-trichloroacetimidate, starting from the known enantiomerically pure diol.     

Sarusubine A, a new dimeric Lythraceae alkaloid from Lagerstroemia subcostata

A new dimeric Lythraceae alkaloid with a cyclobutane ring, sarusubine A (1), has been isolated from the leaves of Lagerstroemia subcostata, and the structure and stereochemistry were elucidated by spectroscopic data.     

Synthesis of brasilibactin A and confirmation of absolute configuration of β-hydroxy acid fragment

A synthesis of brasilibactin A, a cytotoxic siderophore from the actinomycete of Nocardia brasiliensis, and three unnatural diastereomers of the natural product is described. Four possible diastereomers of the β-hydroxy acid fragment were prepared via asymmetric aldol reactions and used to synthesize brasilibactin A and its diastereomers. Careful analysis of ¹H NMR data confirmed that brasilibactin A possesses the 17S,18R absolute stereochemistry.     

A New Phenolic Diglycoside Produced in Response to Copper Toxicity and a New Flavan Dimer from the Leaves of Viburnum ichangense (Hemsl.) Rehd.

A new phenolic digycoside 1 was produced as stress metabolite in the fresh leaves of Viburnum ichangense (Hemsl.) Rehd ., in response to abiotic stress elicitation by CuCl₂. The stress metabolite was characterized as 1‐O‐[α‐L ‐arabinofuranosyl(1→6)‐β‐D ‐glucopyranosyl]‐erythro‐1,2‐bis(4‐hydroxy‐3‐methoxyphenyl)propane‐1,3‐diol ( 1 ). A new flavan dimer, 2,3‐epoxyflavan‐3′,4′,5,7‐tetraol‐(4→8″)‐flavan‐3″,3′′′,4′′′,5′′′,6″‐pentaol ( 2 ), and two known compounds, hovetrichoside A ( 3 ) and asperglaucide ( 4 ), were also isolated. Their structures were established by spectroscopic means.     

Calycilactone A, a novel hexacyclic alkaloid from Daphniphyllum calycillum

A novel Daphniphyllum alkaloid with a rearranged fused-hexacyclic ring system, calycilactone A, was isolated from the leaves of Daphniphyllum calycillum (Daphniphyllaceae), and the structure and relative stereochemistry of the new compound were elucidated on the basis of spectroscopic data.     

Absolute stereochemistries and total synthesis of (+)-arisugacins A and B, potent, orally bioactive and selective inhibitors of acetylcholinesterase

In the current studies, we used the Kakisawa-Kashman modification of the Mosher NMR method to determine the complete absolute stereochemistry of arisugacins. We also report the convergent total synthesis of (+)-arisugacins A and B by a sequence including (i) ruthenium complex-catalyzed asymmetric reduction of the cyclohexenone derivative; (ii) stereoselective construction of the arisugacin skeleton by a Knoevenagel-type reaction of an α,β-unsaturated aldehyde derivative with production of a 4-hydroxy-2-pyrone derivative as a key reaction; and (iii) stereoselective dihydroxylation to give the diol derivative, followed by deoxygenation. Accordingly, we defined the absolute structures of arisugacins A and B as 4a-(R),6a-(R),12a-(R), and 12b-(S). Finally, we characterized the bioactivities of the synthetic intermediates to understand the structure-activity relationships of the arisugacins.     

立体选择性环氧醇还原重排反应研究-环状化合物1,3-二醇的新合成方法

路易斯酸催化下的环氧醇开环重排反应是极为重要的一类反应[1～3], 但是, 至目前所发现的反应都限于控制2个立体中心. 我们在前文[4]中报道了几个环氧醇在异丙醇铝(AIP)的作用下生成1,3-二醇的例子. 最近我们合成了一系列不同结构的底物, 对该反应进行了系统深入的研究, 得出了一些规律性的结果, 即在某些情况下能控制3个立体中心, 别的情况下至少能控制2个立体中心. 该反应还建立了一个立体控制的季碳中心. 我们认为该反应是一个极好的合成手性1,3-二醇特别是螺环二醇的新方法, 对于研究新的不对称反应催化剂具有重要的理论和应用价值[5], 本文对这一反应的初步结果进行了讨论.     

Speradine A, a new pentacyclic oxindole alkaloid from a marine-derived fungus Aspergillus tamarii

A new pentacyclic oxindole alkaloid, speradine A (1), was isolated from the cultured broth of a fungus Aspergillus tamarii, which was separated from driftwood at a seashore in Okinawa. The structure and relative stereochemistry were determined by spectroscopic data and a single crystal X-ray diffraction analysis.     

Synthesis and structure revision of litseaone A

Litseaone A, isolated from the stem barks of Litsea rubescens and Litsea pedunculata, is a chalcone derivative with a novel spiro-epoxide moiety. The structural revision of litseaone A was achieved by the racemic synthesis of the proposed structure and the asymmetric synthesis of the revised structure. The major tautomeric structure of litseaone A and the relative stereochemistry at the epoxide carbon center were also clarified.     

Revised structure of deacetyl-1,10-didehydrosalvinorin G

In comparison with the NMR data of salvinorin A and its 8-epimer, the published structure of deacetyl-1,10-didehydrosalvinorin G was revised to its 8-epimer. The stereochemistry of 8-epi-deacetyl-1,10-didehydrosalvinorin G was further confirmed by NOESY and chemical synthesis.     

Syntheses of cystothiazole A and its stereoisomers: importance of stereochemistry for antifungal activity

The enantiocontrolled total syntheses of all the stereoisomers of a myxobacterial antibiotic, cystothiazole A, are described. The natural syn stereochemistry at the C4-C5 position was controlled by the asymmetric Evans aldol process, whereas the anti relationship was introduced by a modified Evans aldol methodology. Starting with a known aldehyde, the common substrate of the aldol reactions, cystothiazole A and its three stereoisomers were synthesized in 9 steps. All three stereoisomers did not show antifungal activity even at a dosage 2500-fold that of cystothiazole A.     

1,2-Disubstituted cyclohexane nucleosides: comparative study for the synthesis of cis and trans adenosine analogues

A new class of adenosine analogues with 1,2-disubstituted carbocycles (with cis and trans stereochemistry) have been synthesized. Construction of the base on the amino group of (±)-cis-(2-aminocyclohexyl)methanol was more efficient than the Mitsunobu condensation between the purine base and protected (±)-trans-(2-hydroxymethyl)cyclohexanol. The latter strategy gave the final compound with cis stereochemistry in a short number of steps with the overall yield depending on the nature of the protecting group on the hydroxymethyl group of the diol. However, Mitsunobu condensation between a purine base and the protected (±)-cis-(2-hydroxymethyl)cyclohexanol is not an ideal method to obtain trans purine derivatives because the elimination reaction is faster than the substitution reaction.     

Revised structure of tetrapetalone A and its absolute stereochemistry

The chemical structure of tetrapetalone A (1), a novel lipoxygenase inhibitor from Streptomyces sp., was revised by using the ¹H-¹⁵N HMBC technique. Furthermore, the absolute stereochemistry of all the asymmetric carbons in 1 was determined based on the detailed NOE data of 1 and its derivative.     

A short convergent synthesis of the [3.2.1]dioxabicyclooctane subunit of sorangicin A via regioselective epoxide opening

In this paper, we disclose the synthesis of the dioxabicyclo[3.2.1]octane subunit of the potent antibiotic sorangicin A. The synthesis was achieved in a convergent manner in 8 steps. Regio- and stereoselective intermolecular epoxide opening, ring-closing metathesis and iodo-etherification are key steps. cis-2-Butene diol has been employed as a common staring material.     

Total Synthesis of Decahydroquinoline Poison Frog Alkaloids ent-cis-195A and cis-211A

The total synthesis of two decahydroquinoline poison frog alkaloids ent-cis-195A and cis-211A were achieved in 16 steps (38% overall yield) and 19 steps (31% overall yield), respectively, starting from known compound 1. Both alkaloids were synthesized from the common key intermediate 11 in a divergent fashion, and the absolute stereochemistry of natural cis-211A was determined to be 2R, 4aR, 5R, 6S, and 8aS. Interestingly, the absolute configuration of the parent decahydroquinoline nuclei of cis-211A was the mirror image of that of cis-195A, although both alkaloids were isolated from the same poison frog species, Oophaga (Dendrobates) pumilio, from Panama.