Chiral Pool Strategy Research Articles

Synthesis of C1–C9 Domain of the Nominal Didemnaketal A

AbstractBased on chiral pool strategy, a synthesis of the C1–C9 domain of the proposed structure of didemnaketal A, a natural product with potent HIV‐1 protease inhibitory activity, has been achieved. Key transformations are a Sharpless asymmetric dihydroxylation and a chelation‐controlled allylation.

First total synthesis of pro-resolving and tissue-regenerative Maresin sulfido-conjugates

The first stereospecific total synthesis of the pro-resolving and tissue-regenerative Maresin sulfido-conjugates: 13R,14S-MCTR1, 13R,14S-MCTR2 and 13R,14S-MCTR3, derived from docosahexaenoic acid, has been achieved. The key intermediate 13S,14S-epoxy-Maresin methyl ester was synthesized using a chiral pool strategy starting from 2-deoxy-d-ribose. Wittig reactions, selective epoxide formation and epoxide opening with glutathione, l-cysteinylglycine and l-cysteine methyl ester hydrochloride respectively, were the key steps in the synthesis.

ChemInform Abstract: Total Synthesis and Glycosidase Inhibition Studies of (‐)‐Gabosine J and Its Derivatives.

The total syntheses of (–)-gabosine J and its two gabosinol derivatives, the reduced forms of (–)-gabosine J, were achieved by a chiral pool strategy that started from inexpensive and readily available D-mannitol. The desymmetrization of the C2-symmetric tri-O-isopropylidene mannitol through a H2SO4/silica mediated hydrolysis of one of the two terminal ketals and a ring-closing methathesis (RCM) of the appropriately protected diene are the key steps in these syntheses. The preparation of (–)-gabosine J, which involved simple steps as well as inexpensive and readily available reagents and starting material, was completed in 14 steps with an overall yield of 13 %. Similarly, gabosinol J-α and gabosinol J-β (two synthetic derivatives of gabosine J) were prepared in 13 steps in an overall yield of 11 and 6 %, respectively. A preliminary investigation into the biological activity of these compounds revealed that (–)-gabosine J inhibits α-mannosidase with an IC50 of 260 μM. Its reduced form gabosinol J-α inhibits β-galactosidase with an IC50 of 600 μM, and gabosinol J-β inhibits β-glucosidase. This is the first synthesis of a gabosine that employs mannitol as the starting material and the first report of the biological activity of gabosine J.

First total synthesis of the macrophage derived anti-inflammatory and pro-resolving lipid mediator Maresin 2

The first total synthesis of the potent anti-inflammatory lipid mediator Maresin 2 derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C13 and C14 were obtained via a chiral pool strategy from 3,4-O-isopropylidene-2-deoxy-d-ribose. Wittig reactions and acetonide cleavage followed by mild ester hydrolysis afforded Maresin 2.

Total synthesis of the potent anti-inflammatory lipid mediator Protectin D1

The total synthesis of the potent anti-inflammatory lipid mediator Protectin D1 derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C10 and C17 were obtained via a chiral pool strategy from (4R)-4-(2-hydroxyethyl)-2,2-dimethyl-1,3-dioxolane and 3,4-O-isopropylidene-2-deoxy-d-ribose, respectively. Wittig reactions, Takai olefination, Pd0/CuI Sonogashira coupling, and Zn(Cu/Ag) reduction completed the total synthesis of Protectin D1.

Total Synthesis and Glycosidase Inhibition Studies of (–)‐Gabosine J and Its Derivatives

AbstractThe total syntheses of (–)‐gabosine J and its two gabosinol derivatives, the reduced forms of (–)‐gabosine J, were achieved by a chiral pool strategy that started from inexpensive and readily available D‐mannitol. The desymmetrization of the C2‐symmetric tri‐O‐isopropylidene mannitol through a H2SO4/silica mediated hydrolysis of one of the two terminal ketals and a ring‐closing methathesis (RCM) of the appropriately protected diene are the key steps in these syntheses. The preparation of (–)‐gabosine J, which involved simple steps as well as inexpensive and readily available reagents and starting material, was completed in 14 steps with an overall yield of 13 %. Similarly, gabosinol J‐α and gabosinol J‐β (two synthetic derivatives of gabosine J) were prepared in 13 steps in an overall yield of 11 and 6 %, respectively. A preliminary investigation into the biological activity of these compounds revealed that (–)‐gabosine J inhibits α‐mannosidase with an IC50 of 260 μM. Its reduced form gabosinol J‐α inhibits β‐galactosidase with an IC50 of 600 μM, and gabosinol J‐β inhibits β‐glucosidase. This is the first synthesis of a gabosine that employs mannitol as the starting material and the first report of the biological activity of gabosine J.

Expedient Synthesis of (R)‐Curcuphenol: A Chiral Pool Strategy

AbstractCurcuphenol is an interesting sesquiterpenoid with diverse bioactivities. Exploration of a concise and scalable synthetic route is still of significance in spite that many asymmetric total syntheses have been achieved. We report an expedient asymmetric synthesis of (R)‐curcuphenol from citronellal, which features only two purification operations in the overall six‐step synthesis.

Total synthesis of Resolvin D1, a potent anti-inflammatory lipid mediator

The total synthesis of Resolvin D1, a potent endogenous anti-inflammatory lipid mediator derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-groups at C7, C8 and C17 were obtained via a chiral pool strategy from 2-deoxy-d-ribose. Wittig reactions followed by a modified Pd0/CuI Sonogashira coupling and Zn(Cu/Ag) cis-reduction completed the total synthesis of Resolvin D1.

Total synthesis of the macrophage derived anti-inflammatory lipid mediator Maresin 1

The total synthesis of Maresin 1, an endogenous macrophage pro-resolving lipid mediator derived from docosahexaenoic acid, has been achieved. The chiral hydroxy-group at C7 was obtained via a Jacobsen hydrolytic kinetic resolution of a terminal epoxide whereas the center at C14 arises from a chiral pool strategy starting from 2-deoxy-d-ribose. Pd0/CuI Sonogashira coupling of the two key fragments and Zn(Cu/Ag) reduction completed the total synthesis of Maresin 1.

ChemInform Abstract: A Chiral Pool Strategy for the Synthesis of Enantiopure Hydroxymethyl‐Substituted Pyridine Derivatives.

AbstractThe method is based on the TmsOTf‐promoted cyclocondensation of β‐ketoenamides.

Synthesis of stagonolide C from Mulzer epoxide

Total synthesis of stagonolide C using chiral pool strategy is described. The two key intermediates were prepared from l-glutamic acid and d-glucono-1,5-lactone, followed by Julia–Lythgoe olefination and Yamaguchi esterification to afford the target compound in an efficient way.

A Chiral Pool Strategy for the Synthesis of Enantiopure Hydroxymethyl‐Substituted Pyridine Derivatives

AbstractA simple procedure for the synthesis of enantiopure hydroxymethyl‐substituted pyridine derivatives is presented. The developed method is based on TMSOTf‐promoted cyclocondensations of β‐ketoenamides, leading to differently substituted 4‐hydroxypyridine/4‐pyridone derivatives. The required β‐ketoenamides were prepared by acylation ofeasily available enamino ketones with suitably protected enantiopure carboxylic chlorides. Most of the experiments were performed withD‐mandelic acid as starting material. It has been shown that all steps occur essentially without racemisation. Several of the prepared 4‐pyridone derivatives were transformed into the corresponding pyrid‐4‐yl nonaflates and subjected to a series of palladium‐catalysed transformations, such as Suzuki, Heck or Sonogashira reactions. In addition, regioselective side‐chain functionalisation of unsymmetrically 2,6‐disubstituted pyridine derivatives was accomplished by application of Boekelheide rearrangements of the corresponding pyridineN‐oxides. The presented methods allow a flexible, rapid and scalable approach to highly substituted, enantiopure pyridine derivatives.

Synthesis of MLN4924

MLN4924 is an adenosine monophosphate mimic that inhibits the NEDD8 activating enzyme resulting in S-phase defects, DNA damage, and apoptosis. It is currently in phase I clinical trials for the treatment of various cancers. The enantiospecific synthesis depicted is based on a chiral pool strategy that begins with d-ribose.

A new short synthesis of 10 R-tuberculostearic acid and its enantiomer

Tuberculostearic acid (10 R-methyloctadecanoic acid) and its 10 S-enantiomer were synthesised by a chiral pool strategy, in four steps from citronellyl bromide.

First total synthesis of 7( S),16( R),17( S)-Resolvin D2, a potent anti-inflammatory lipid mediator

The first total synthesis of 7( S),16( R),17( S)-Resolvin D2, a lipid mediator derived from docosahexaenoic acid, has been achieved. The key features of our synthetic strategy encompass a Co-salen hydrolytic kinetic resolution of a terminal epoxide combined with a chiral pool strategy.

Formal Total Synthesis of (+)‐Salicylihalamides A (Ia) and B (Ib): A Combined Chiral Pool and RCM Strategy.

ChemInformVolume 35, Issue 21 Natural Products Formal Total Synthesis of (+)-Salicylihalamides A (Ia) and B (Ib): A Combined Chiral Pool and RCM Strategy. KyoungLang Yang, KyoungLang Yang Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorBurchelle Blackman, Burchelle Blackman Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorWibke Diederich, Wibke Diederich Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorPatrick T. Flaherty, Patrick T. Flaherty Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorCraig J. Mossman, Craig J. Mossman Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorSubho Roy, Subho Roy Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorYu Mi Ahn, Yu Mi Ahn Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorGunda I. Georg, Gunda I. Georg Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this author KyoungLang Yang, KyoungLang Yang Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorBurchelle Blackman, Burchelle Blackman Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorWibke Diederich, Wibke Diederich Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorPatrick T. Flaherty, Patrick T. Flaherty Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorCraig J. Mossman, Craig J. Mossman Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorSubho Roy, Subho Roy Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorYu Mi Ahn, Yu Mi Ahn Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this authorGunda I. Georg, Gunda I. Georg Dep. Med. Chem., Univ. Kans., Lawrence, KS 66045, USASearch for more papers by this author First published: 29 April 2004 https://doi.org/10.1002/chin.200421212Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume35, Issue21May 25, 2004 RelatedInformation

Formal total synthesis of (+)-salicylihalamides A and B: a combined chiral pool and RCM strategy.

The formal total synthesis of the (+)-salicylihalamides A and B is detailed, utilizing a chiral pool approach to generate the three stereogenic centers and a ring-closing metathesis (RCM) for the formation of the macrocyclic ring structure. Starting from a known glucose-derived alcohol, the formal total synthesis was achieved in an efficient 13-step protocol in 26% overall yield. It was found that substitution at the remote phenolic group significantly influenced the ratio of the E- and Z-double bond products in the RCM step. The introduction of phenol protecting groups provided E-isomers preferentially and also enhanced the rates of the RCM reactions.

Total synthesis of aspirin-triggered 15- epi-lipoxin A 4

The total synthesis of aspirin-triggered 15- epi-LXA 4 has been achieved using a chiral pool strategy for the C1–C12 fragment starting from 2-deoxy- d-ribose. Sharpless catalytic AE generated the C15 chiral center with >98% ee. The stereospecific ( Z)-reduction of the conjugated trienyne to the tetraene was achieved with Zn(Cu/Ag) in aq. CH 3OH at rt.