Yoshiyasu Ichikawa

Synthesis of C-glycosyl compounds from 3,4,6-tri-O-acetyl-1,5-anhydro-D-arabino-hex-1-enitol and allyltrimethylsilane and bis(trimethylsilyl)acetylene

Abstract C -Glycosyl derivatives of compounds bearing two, three, or four carbon atoms were obtained from 3,4-6-tri- O -acetyl-1,5-anhydro- d - arabino -hex-1-enitol ( 1 ) via a deacetoxylated oxonium ion generated by treatment with a Lewis acid. The nucleophilic reagents with this cation were bis(trimethylsilyl)acetylene, allyltrimethylsilane, and furan, which were found to exhibit a higher reaction velocity that 1 itself, a potential nucleophile leading to polymerization.

Synthesis of a marine polyether toxin, okadaic acid [4]p1 -- total synthesis

Abstract Three segments A, B and C for okadaic acid synthesis were coupled with each other in the order of A+(B+C), the key steps of the twice couplings being between sulfone carbanions and aldehydes. After the B+C coupling, the asymmetric center C-27 was generated by a hydride reduction of the corresponding ketone 16 under electronic control. The second coupling was followed to form the C- 14 15 double bond. Oxidation of the α-oxy aldehyde 36 into the carboxylic acid group was achieved with sodium chlorite without C-1/C-2 bond cleavage. The total synthesis of okadaic acid was accomplished in 106 steps from commercially available D-glucose derivatives and butyne-diol.

Acyclic stereocontrol by heteroconjugate addition—4 : Anti-diastereoselection by a β-chelation effect

Abstract High selectivity in heteroconjugate addition for C—C bond formation with complete syndiastereoselection has been attributed to the chelation effect between the α-oxygen atom of the substrate and the nucleophile anions through metal cations. Herein is described a new method exhibiting antidiastereoselection based on a different chelation effect caused by the ligands on the β-carbon atom to the heteroolefin. Most of the examples are taken as the heteroolefin connected at the C-5 position to D-hexopyranosides with a C-4 hydroxyl group. Thus, the methodology was expanded to an optically active system starting from glucose as a chiral source for asymmetric synthesis. The results are very clear in the case of a Grignard reagent as the nucleophile instead of methyllithium, and so one of the compounds was used for the synthesis of the A-segment of okadaic acid.

Synthesis of a marine polyether toxin, okadaic acid [1] — strategy and synthesis of segment a

Abstract The title compound was divided into three retrosynthetic segments A, B and C, by disconnecting two C-C bonds at C- 14 15 and C- 27 28 . Segment A for okadaic acid synthesis comprises the carbon skeleton from C-1 through C-14, which was further disconnected at the bonds between C-8 and C-9 into two fragments A1 and A2. Each fragment was synthesized in the optically active form from D-glucose derivatives. Key steps are the oxymercuration and anti-selective heteroconjugate addition to elaborate the asymmetric carbons on acyclic parts of these fragments. The coupling was facilitated between the acetylenic carbanion and the lactone carbonyl of the respective fragments. The segment A was synthesized in 36 steps.

Synthetic studies toward marine toxic polyethers [5] the total synthesis of okadaic acid

Abstract The total synthesis of okadaic acid has been accomplished through the coupling of all the segments, A, B and C, by means ofsulfone-carbanion strategy.

Total synthesis of (+)-prelog-djerassi lactonic acid

Optically active Prelog-Djerassi Lactonic Acid 1 was synthesized from D-glucal: the crucial point being the elaboration of the carboxylic group as shown in eq. 1 and 2 which involve the sequential process [i] asymmetric addition of methyl anion onto the hetero-olefin 2, [ii] trapping the carbanion intermediate 3 [E=Li to SePh] and [iii] oxidative hydrolysis of 3 via sila-pummerer rearrangement into 4.

Synthesis of a marine polyether toxin, okadaic acid (2) — synthesis of segment b

Abstract The central synthetic segment B for okadaic acid comprises the carbons from 15 through 27 including 6 asymmetric carbons. Its synthesis started from a D-Glucose derivative, whose carbon was extended twice for the six and five membered etherial ring formation. The original conformation of the sugar was inverted when the spiro-ether was formed to eventuate the axial aldehyde formation in 35 overall steps.

Synthesis of a marine polyether toxin, okadaic acid (3) — synthesis of segment c

Abstract The title compound was divided into three retrosynthetic segments, A, B and C, by disconnecting two C-C bonds at C- 14 15 and C- 27 28 . Synthesis of the segment C in the optically active natural form starting from a D-glucose derivatives is described. The key features are stereochemical control which includes a methodology named heteroconjugate addition involving carbon chain extension using carbanion stabilized by phenylsulfonyl group.

Acyclic stereocontrol by heteroconjugate addition — 3 : Diastereoselective synthesis of either syn or anti diastereoisomer

Abstract A stereoselective synthesis of both syn- and anti-diastereoisomers (3 and 4) was established by a method involving heteroconjugate addition, as the key step, with various nucleophiles such as alkoxyvinyllithiums which can be functionalized after the addition. Two examples with aliphatic and carboxylic groups are demonstrated in high specificity.

Synthetic studies toward marine toxic polyethers (2) synthesis of the B-segment of okadaic acid and coupling with the C-segment

Abstract Part of okadaic acid 1a was synthesized stereoselectively in the form of 4a (involving C-16 through C-38 with 10 asymmetric carbons), by coupling the equivalents of 2 and 3 as the synthetic segments B and C (Scheme 1), the former being prepared via 12 and 6 from a D-glucopyranose derivative (Scheme 2).