Studies towards the total synthesis of batzelladine A

Application of a diastereoselective three-component coupling to the bicyclic core of the batzelladine alkaloids is described. The synthesis features the elaboration of glutamic acid by use of Eschenmoser sulfide contraction. An earlier approach is also included, which shows some limitations of dithiane chemistry when applied to the particular compounds required for this target.     

Enantioselective synthesis of the C-14 to C-5 cyclopentane segment of jatrophane diterpenes

The enantioselective synthesis of the C-14 to C-5 cyclopentane segment of jatrophane diterpenes is reported. An Evans aldol addition, a Horner-Wadsworth-Emmons olefination and a thermal intramolecular carbonyl ene reaction of an α-keto ester served as key C/C-connecting transformations.     

Application of the AAA reaction to the synthesis of the furanoside of C-2-epi-hygromycin A: a total synthesis of C-2-epi-hygromycin A

A strategy for stereocontrolled syntheses of furanoside type of natural products is developed for a glycosyl aryl ether. This strategy resolves the issue of low diastereoselectivity typical of normal glycosidation methods for furanosides. All the stereochemistry ultimately derives from a desymmetrization of a 2,5-diacyloxy-2,5-dihydrofuran using Pd catalyzed asymmetric allylic alkylation which sets both the absolute stereochemistry and 1,4-relative stereochemistry. Diastereo-controlled elaboration of the 3,4-double bond then completes the synthesis. A new conjunctive reagent, 1-nitro-1-phenylsulfonyl-ethane, is developed to serve as an acyl anion equivalent. The utility of a phenol as a nucleophile in the Pd catalyzed glycosylation is demonstrated. From this strategy emerged a short, practical synthesis of C-2-epi-hygromycin A.     

Studies toward the total synthesis of popolohuanone E: enantioselective synthesis of 8-O-methylpopolohuanone E

[structure: see text]. 8-O-methylpopolohuanone E (2) was synthesized in a highly convergent manner starting from the cis-fused decalin derivative accessible from the (-)-Wieland-Miescher ketone analogue. The synthetic method features a biogenetic-type annulation of the phenolic and quinone segments to regioselectively construct the central tricyclic ring system as the key step.     

Exploratory studies aimed at a synthesis of vinigrol. 4. Probe of possible means for direct connection of the side arms and of ring-contraction alternatives

Attempts have been made to gain access to the vinigrol structural framework by way of three routes. These include reductive transannular cyclization, adaptation of the Ramberg-Backlund rearrangement, and deployment of the lactam-sulfoxide ring contraction protocol. While the first of these options involves direct transannular C-C bond formation, the other two embody the concept of larger ring construction as a prelude to ring contraction. The initial installation of a sulfur atom involves prior thiacyclononane formation, a process believed to be potentially easier to accomplish. However, arrival at 13, 14, or 17 was not achieved. Installation of the heterocyclic ring contained in 31 proved to be equally problematic. Increased disassembly of the molecular structure as featured in dibromide 20 did allow for direct conversion to sulfone 22. This advanced building block proved not be conducive to in situ alpha-chlorination and extrusion of the sulfur atom.     

Studies toward the synthesis of pinolidoxin, a phytotoxic nonenolide from the fungus Ascochyta pinodes. Determination of the configuration at the C-7, C-8, and C-9 chiral centers and stereoselective synthesis of the C(6)-C(18) fragment

The absolute stereochemistry at the C-7, C-8, and C-9 chiral centers of pinolidoxin (1) has been determined by chemical and spectral methods. First, the synthesis of four stereoisomeric fully benzoylated 2,3-erythro-1,2,3,4-heptanetetrols, corresponding to the C(6)-C(18) portion of the natural substance, has been accomplished starting from meso-tartaric acid. As next step, the selection of the synthetic tetrabenzoate possessing "natural" stereochemistry (10a'), suitable for absolute configuration determination, has been carried out by correlation with its "natural" homologue derived from degradation of pinolidoxin. Determination of the stereochemistry at the title chiral centers has been carried out by application of the Mosher's method both to 7a', a compound stereochemically related to 10a', and to pinolidoxin itself. The stereoselective synthesis of a protected form of the C(6)-C(18) portion of pinolidoxin, to be used in its total synthesis, has also been accomplished starting from commercially available D-erythronolactone.     

Studies towards the total synthesis of hygrocins A and B

The western segment of hygrocins A–B has been synthesized through the coupling of a chiral C5–C13 synthon with the sterically demanding hexasubstituted naphthalenic core. The C5–C13 chiral fragment has been assembled via a stereoselective Johnson orthoester rearrangement of an optically pure allylic alcohol derived from d-glucose. Our studies lay the platform for the determination of the absolute configuration of the unassigned C8-stereocenter of the title compounds in addition to the completion of the total synthesis of the unique ansamacrolides hygrocins A and B.     

Studies directed toward the total synthesis of discodermolide: asymmetric synthesis of the C1-C14 fragment

[structure: see text] A convergent and stereoselective assembly of the C1-C14 subunit of marine natural product (+)-discodermolide has been completed. The approach employs chiral allylsilane bond construction methodology to establish four of the eight stereogenic centers. Key fragment coupling is achieved via an efficient stereoselective acetate aldol reaction between C1-C6 and C7-C14 subunits.     

Studies towards the stereoselective total synthesis of Gliomasolide A

The first synthetic approach towards the Gliomasolide A is described in 15 linear steps with 4% overall yield. The key steps in this approach are RCM protocol for the construction of 14-member macrolide, a Sharpless kinetic resolution, Keck and Brown’s allylations for the installation of desired stereocenters.     

Microwave-assisted Allylic Oxidation at C-13 Position of 14-Deoxysinenxan A

Microwave-assisted allylic oxidation at C-13 position of 14-deoxysinenxan A was described. This new method (150℃/10 min/5 bar on microwave synthesizer) led to a better yield of compound 1 and shorter reaction time.     

Studies toward the total synthesis of vinigrol. synthesis of the octalin ring

[reaction: see text] Herein, we disclose our results regarding various strategies toward the assembly of the octanyl ring of vinigrol. Attempts to generate the problematic eight-membered ring through a ring expansion or via unification of the terminal olefins using the ring-closing metathesis were not successful. The cyclooctane ring was created via a sequential hydroxy Diels-Alder/Claisen rearrangement reaction of diene 55 and N-benzylmaleimide.     

Studies on the total synthesis of streptazolin and its related natural products: first total synthesis of (+/-)-8alpha-hydroxystreptazolone

The intramolecular Pauson-Khand reaction of 2-oxazolone derivatives with a suitable heptynyl appendage gave exclusively the corresponding 4-hydroxy-6-substituted-9-oxa-1-azatricyclo[6.2.1.0(5,11)]undec-5-ene-7,10-diones. On the basis of this newly developed Pauson-Khand reaction of 2-oxazolone-alkyne derivatives, the first total synthesis of (+/-)-8alpha-hydroxystreptazolone was accomplished in a highly stereoselective manner. In addition, (+/-)-7-epi-8alpha-hydroxystreptazolone was also synthesized.