MPM (4-methoxybenzyl) protection of hydroxy functions under mild acidic conditions
TL;DR: In this paper, a mild protection method for hydroxy functions with a MPM (4methoxybenzyl) group, various types of hydroxy compounds were treated with MPM trichloroacetimidate in the presence of an acid catalyst.
About: This article is published in Tetrahedron Letters.The article was published on 1988-01-01. It has received 216 citations till now.
Citations
More filters
TL;DR: This data indicates that the phytochemical properties of Aplysiatoxin-like substances have changed significantly since their discovery in the 1970s, and these changes have implications for the design of new drugs and their application in medicine.
Abstract: 1. Intoduction 4348 2. Oxolane Macrodiolides 4348 2.1. Pamamycin 607 (1) 4348 2.1.1. Thomas Total Synthesis20 4349 2.1.2. Lee Total Synthesis28 4351 2.1.3. Metz Total Synthesis35 4353 2.1.4. Kang Total Synthesis41 4354 2.2. Amphidinolide X (2) 4356 2.2.1. Fürstner Total Synthesis59 4356 3. Oxane/Oxene Macrodiolides 4359 3.1. SCH 351448 (3) 4359 3.1.1. Lee Total Synthesis71 4359 3.2. Swinholide A (4) 4360 3.2.1. Paterson Total Synthesis82 4360 3.2.2. Nicolaou Total Synthesis83 4360 4. Cyclic Acetal Macrodiolides 4362 4.1. Cycloviracin B1 (5) 4362 4.1.1. Fürstner Total Synthesis96 4363 4.2. Glucolipsin A (6) 4366 4.2.1. Fürstner Total Synthesis117 4366 5. Cyclic Hemiketal Macrodiolides 4368 5.1. Boromycin (7) 4368 5.1.1. White Total Synthesis123 4368 5.2. Tartrolon B (8) 4369 5.2.1. Mulzer Total Synthesis130 4370 5.3. Debromoaplysiatoxin (9) and Aplysiatoxin (10) 4373 5.3.1. Kishi Total Synthesis142 4373 6. Conclusions 4375 7. Acknowledgments 4375 8. References 4375
256 citations
TL;DR: An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale.
Abstract: An efficient, highly convergent, stereocontrolled total synthesis of the potent antimitotic agent (+)-discodermolide (1) has been achieved on gram scale. Key elements of the successful strategy include (1) elaboration of three advanced fragments from a common precursor (CP) which embodies the repeating stereochemical triad of the discodermolide backbone, (2) σ-bond installation of the Z trisubstituted olefin, exploiting a modified Negishi cross-coupling reaction, (3) synthesis of a late-stage phosphonium salt utilizing high pressure, and (4) Wittig installation of the Z disubstituted olefin and the terminal (Z)-diene.
220 citations
TL;DR: In this paper, a practical stereocontrolled synthesis of (+)-discodermolide (1) has been completed in 10.3% overall yield (23 steps longest linear sequence).
Abstract: A practical stereocontrolled synthesis of (+)-discodermolide (1) has been completed in 10.3% overall yield (23 steps longest linear sequence). The absolute stereochemistry of the C(1)-C(6) (7), C(9)-C(16) (8), and C(17)-C(24) (9) subunits was established via substrate-controlled, boron-mediated, aldol reactions of the chiral ethyl ketones 10, 11, and 12. Key fragment coupling reactions were a lithium-mediated, anti-selective, aldol reaction of aryl ester 8 (under Felkin-Anh induction from the aldehyde component 9), followed by in situ reduction to produce the 1,3-diol 40, and a (+)-diisopinocampheylboron chloride-mediated aldol reaction of methyl ketone 7 (overturning the inherent substrate induction from the aldehyde component 52) to give the (7S)-adduct 58. The flexibility of our overall strategy is illustrated by the synthesis of a number of diastereomers and structural analogues of discodermolide, which should serve as valuable probes for structure-activity studies.
193 citations
TL;DR: The research reported herein represents an important step toward the preparation of functional mesostructures with controlled helical architectures and shows the benefits of reducing the nonfunctional part of the molecule, in this case with short chiral isopentyl chains.
Abstract: The controlled preparation of chiral structures is a contemporary challenge for supramolecular science because of the interesting properties that can arise from the resulting materials, and here we show that a synthetic nonamphiphilic C3 compound containing π-functional tetrathiafulvalene units can form this kind of object. We describe the synthesis, characterization, and self-assembly properties in solution and in the solid state of the enantiopure materials. Circular dichroism (CD) measurements show optical activity resulting from the presence of twisted stacks of preferential helicity and also reveal the critical importance of fiber nucleation in their formation. Molecular mechanics (MM) and molecular dynamics (MD) simulations combined with CD theoretical calculations demonstrate that the (S) enantiomer provides the (M) helix, which is more stable than the (P) helix for this enantiomer. This relationship is for the first time established in this family of C3 symmetric compounds. In addition, we show th...
140 citations
TL;DR: Fostriecin (CI-920, 1; see Scheme 1) is a structurally interesting antitumor agent that was first isolated in 1983 by scientists at Warner Lambert-Parke Davis as discussed by the authors.
Abstract: Fostriecin (CI-920, 1; see Scheme 1) is a structurally interesting antitumor agent that was first isolated in 1983 by scientists at Warner Lambert-Parke Davis.[1] It displays in vitro activity against a broad range of cancerous cell lines as well as in vivo antitumor activity,[2] and it appears to operate by a novel mechanism involving inhibition of the mitotic entry checkpoint.[3] In this context, fostriecin is a potent inhibitor of protein serine/threonine phosphatases, and it is in fact the most selective protein phosphatase inhibitor identified to date (104 times greater affinity for the protein phosphatases PP2A and PP4 versus PP1).[4] It was not until 1997 that a correct and complete stereochemical assignment of fostriecin was made by Boger and coworkers,[5] and that was followed very recently by a report of the first total synthesis from the same group.[6] Certainly, the development of a practical synthetic route to fostriecin is warranted based on its interesting biological properties. In addition, clinical trials carried out at the National Cancer Institute were halted early in Phase I over concerns about the stability and purity of the natural material.[7] A flexible synthetic route to 1 could serve as a basis for the discovery of analogues with similar biological but more desirable physical properties. In addition, the structure of fostriecin poses an assortment of interesting challenges to an efficient synthetic design, including the presence of the unsaturated lactone,[8] the C8 ± C11 triol monophosphate component, and the conjugated Z,Z,E-trienol unit. Herein we report a new total synthesis of fostriecin. Our approach integrates highly effective asymmetric catalytic reactions to generate key chiral building blocks, and efficient coupling reactions to enable their convergent assembly. The synthetic plan involves assembly of four fragments (2 ± 5) of similar complexity (Scheme 1). Epoxyketone 3 plays a central role in our strategy, serving not only as the source of
123 citations
References
More filters
TL;DR: Emphasis is placed on glycoside and saccharide formation by 1-O-alkylation, on the trichloroacetimidate method, and on activation through the formation of glycosylsulfonium salts and Glycosyl fluorides.
Abstract: Glycoproteins, glycolipids, and glycophospholipids (glycoconjugates) are components of membranes. The oligosaccharide residue is responsible for intercellular recognition and interaction; it acts as a receptor for proteins, hormones, and viruses and governs immune reactions. These significant activities have stimulated interest in oligosaccharides and glycoconjugates. With their help it should be possible to clarify the molecular basis of these phenomena and to derive new principles of physiological activity. Major advances in the synthesis of oligosaccharides have been made by the use of the Koenigs-Knorr method, in which glycosyl halides in the presence of heavy-metal salts are employed to transfer the glycosyl group to nucleophiles. The disadvantages of this procedure have led to an intensive search for new methods. Such methods will be discussed in this article. Emphasis is placed on glycoside and saccharide formation by 1-O-alkylation, on the trichloroacetimidate method, and on activation through the formation of glycosylsulfonium salts and glycosyl fluorides.
1,185 citations
TL;DR: Methoxybenzyl protecting groups of alcohols were readily and efficiently removed with DDQ in CH2Cl2-H2O at room temperature under these neutral conditions, other usual protecting groups, isopropylidene, methoxymethyl, benzyloxymmethyl, tetrahydropyranyl, acetyl, t-butyldimethylsilyl, benyl, benzoyl, and tosyl, as well as functional groups, epoxide, double bond, and ketone, were remained unchanged as discussed by the authors.
546 citations
TL;DR: In this paper, the 4-methoxybenzyl (MPM) protecting group for hydroxy functions is readily removed with DDQ in dichloromethane containing a small amount of water at room temperature.
460 citations
TL;DR: In this paper, the MPM protecting group for hydroxy function was selectively removed by catalytic hydrogenolysis with Raney nickel in the presence of the DMPM protecting groups, and applied to the synthesis of some synthons to macrolide and polyether antibiotics.
70 citations
TL;DR: The DMPM (3,4-dimethoxybenzyl) protection for hydroxy function was deprotected more readily than the MPM protection by DDQ oxidation under neutral conditions, and applied to the synthesis of some synthons to macrolide and polyether antibiotics as mentioned in this paper.
66 citations