Stereoselective Syntheses of Rolliniastatin 1, Rollimembrin, and Membranacin

2.2. Chiral Imines and Imine Derivatives 2.2.1. Imines and Imine Derivatives from Chiral Carbonyl Compounds. Chiral α-oxysubstituted aldehydes were used by Kobayashi and co-workers in a three-component reaction with allylboropinacolate and ammonia in ethanol. The corresponding homoallylic primary amines were obtained with good to high syn diastereofacial selectivities (Scheme 5). 20 The precise reaction mechanism was unclear. Preformation of N-Scheme 3 Scheme 4 Scheme 5 Chemical Reviews Review dx.

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“…174 The corresponding homoallylic alcohols were obtained in high yield and stereoselectivity (>99:1 dr).…”

Section: Synthesis Of Natural Productsmentioning

confidence: 96%

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

2013

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“…They have been frequently applied to synthesis of a variety of significant pharmaceuticals and natural products. [2][3][4][5][6][7][8][9][10][11][12][13] However, their commercial availability is still limited and quite expensive, and they are more commonly available as the corresponding potassium salts. In particular, monomethyl malonate became commercially available only last year, but is expensive, or the purities are typically less than 99%, such as 96%.…”

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confidence: 99%

Practical Large Scale Synthesis of Half-Esters of Malonic Acid

Niwayama

Cho

2009

Chem. Pharm. Bull.

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Half-esters of malonic acid such as monomethyl malonate and monoethyl malonate are very important building blocks. They have been frequently applied to synthesis of a variety of significant pharmaceuticals and natural products. [2][3][4][5][6][7][8][9][10][11][12][13] However, their commercial availability is still limited and quite expensive, and they are more commonly available as the corresponding potassium salts. In particular, monomethyl malonate became commercially available only last year, but is expensive, or the purities are typically less than 99%, such as 96%. Therefore, development of a more efficient synthetic method for monoalkyl malonates on a large scale is essential.One method for preparation of half-esters is monosaponification of symmetric diesters, but successful distinction of the two identical ester groups remains challenging. In fact, monosaponification typically produces a dirty mixture of the starting diester, the corresponding halfester, and the diacid, even with the use of one equivalent of a base. In particular, the synthesis of half-esters of malonic acid is still difficult especially on a large scale, because of potential decarboxylation. Only a limited number of examples of monosaponification of dimethyl or diethyl malonate have been reported, [14][15][16] but they require a long time and more than one step. Some modified methods are reported applying Meldrum's acid, 17,18) but Meldrum's acid is costly and not suitable for large-scale production of monoalkyl malononate. The enzymatic monohydrolysis of dialkyl malonates reported utilizes an enzyme not commercially available. 19) Other methods by carbalkoxylation of malonic acid are also reported, but the yields are rather modest. 20)Herein we describe a large-scale synthesis of monomethyl malonate and monoethyl malonate applying the selective monohydrolysis of symmetric diesters we reported before. Earlier, we reported a selective monohydrolysis that enables a series of symmetric diesters with the use of an aqueous NaOH or KOH and a co-solvent such as tetrahydrofuran (THF) or CH 3 CN at 0°C (Chart 1).21) This reaction is practical, mild, and environmentally benign, and has been of interest in process chemistry, exhibiting the potential of scaling up. The selectivity of this reaction was initially found to be particularly high for cyclic 1,2-diesters with the two ester groups in close proximity, even with the use of almost 2 equivalents (or greater) of the base, producing the corresponding half-esters in near-quantitative yields. We reasoned that electrostatic attractive interaction between the two closely located carbonyl groups may play a role in this high selectivity. We recently modified the conditions of this reaction and applied them to monohydrolysis of a series of dialkyl malonates and their derivatives on the scale of 1.2 mmol. 22) They show that the yields are around 80% to near quantitative. Here we examined the possibility of scaling up this reaction, focusing on monomethyl malonate and monoethyl malonate, which are among...

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“…CM reactions were performed with three to four molar equivalents of either butenolide 17 xxiii,xxiv or the respective carbohydrate alkene partner 18 - 23 using 10 mol% Grubbs 2 nd generation catalyst (Table 1). xxv,xxvi In general, it was more practical to use the carbohydrate alkene (vs the butenolide alkene), as the limiting reactant reagent for two reasons.…”

Section: Resultsmentioning

confidence: 99%

“…A solution of 18 (155 mg, 0.3 mmol) and butenolide 17 xxiii,xxiv (20 mg, 0.1 mmol) in DCM (8 mL) was degassed using N 2 for 30 min and then Grubb's II catalyst (9 mg, 0.01 mmol) was added. The reaction was stirred for 18 h and then concentrated in vacuo.…”

Section: Methodsmentioning

confidence: 99%

Synthesis and anti-tumor activity of carbohydrate analogues of the tetrahydrofuran containing acetogenins

Bachan

Tony

Kawamura

et al. 2013

Bioorganic & Medicinal Chemistry

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The tetrahydrofuran (THF) containing annonaceous acetogenins (AAs) are attractive candidates for drug development because of their potent cytotoxicity against a wide range of tumors and their relatively simple and robust structures. Replacement of the THF segment with a sugar residue may deliver analogues with improved tumor selectivity and pharmacokinetics and are therefore attractive for drug development. As a first test to the feasibility of such structures, a set of such monosaccharide analogues was synthesized and assayed against four human tumor cell lines, cervical (HeLa), breast (MDA-MB231), T-cell leukemia (Jurkat) and prostate (PC-3). Certain analogues showed low micromolar activity that was comparable to a structurally similar, naturally occurring mono-THF acetogenin. A preliminary examination of the structure-activity profile of these carbohydrate analogues suggests that they have a similar mechanism of action as their THF congeners.

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Stereoselective Syntheses of Rolliniastatin 1, Rollimembrin, and Membranacin

Abstract: A radical cyclization of beta-alkoxyvinyl sulfoxides-Pummerer rearrangement-allylation protocol was successfully applied to the synthesis of the threo/cis/threo/cis/erythro bis-oxolane moiety in rolliniastatin 1 (1), rollimembrin (2), and membranacin (3).

Cited by 53 publications

References 14 publications

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

Practical Large Scale Synthesis of Half-Esters of Malonic Acid

Synthesis and anti-tumor activity of carbohydrate analogues of the tetrahydrofuran containing acetogenins

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