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"Chiral pool" compounds possessing well defined stereocenters and suitable functionality serve as excellent building blocks for the synthesis of natural products and therapeutically important compounds. Tartaric acid is a C2 -symmetric molecule available in both enantiomeric forms. It was extensively utilized in the synthesis of privileged chiral ligands/catalysts such as TADDOLs, and as a start point in the synthesis of plethora of compounds. The advent of several new C-C bond forming reactions offers opportunity for the development of novel synthetic strategies based on chiral pool compounds. We found that the desymmetrization of the bis-dimethyl amide/Weinreb amide derived from tartaric acid can be accomplished by controlled addition of Grignard /organolithium reagents leading to the mono keto amides, the reduction of which affords the γ-hydroxy amides. This account describes our research efforts of more than a decade on the synthesis and application of diverse γ-hydroxy amides derived from tartaric acid in the total synthesis of structurally simple to complex bio-active natural products.

Angiogenesis is a hallmark of cancer, promoting growth and metastasis. Anti‐angiogenic treatment has limited efficacy due to therapy‐induced blood vessel alterations, often followed by local hypoxia, tumor adaptation, progression, and metastasis. It is therefore paramount to overcome therapy‐induced resistance. We show that Apelin inhibition potently remodels the tumor microenvironment, reducing angiogenesis, and effectively blunting tumor growth. Functionally, targeting Apelin improves vessel function and reduces polymorphonuclear myeloid‐derived suppressor cell infiltration. Importantly, in mammary and lung cancer, Apelin prevents resistance to anti‐angiogenic receptor tyrosine kinase (RTK) inhibitor therapy, reducing growth and angiogenesis in lung and breast cancer models without increased hypoxia in the tumor microenvironment. Apelin blockage also prevents RTK inhibitor‐induced metastases, and high Apelin levels correlate with poor prognosis of anti‐angiogenic therapy patients. These data identify a druggable anti‐angiogenic drug target that reduces tumor blood vessel densities and normalizes the tumor vasculature to decrease metastases.

A novel ring contraction/rearrangement sequence leading to functionalized 2,8-oxymethano-bridged di- and triquinane compounds is observed in the reaction of various substituted 1-methyl-4-isopropenyl-6-oxabicylo[3.2.1]octan-8-ones with Lewis acids. The reaction is novel and is unprecedented for the synthesis of di- and triquinane frameworks.

Aim This study examines possible predictors of physical and social functioning in adolescents with rheumatological conditions. Condition-related variables and psychosocial variables were studied, and their relative contribution as predictors was examined. Methods The study population was one hundred and twelve adolescents (11–18 years) attending secondary and tertiary paediatric rheumatology outpatient clinics in south-west England. These adolescents completed validated self-report accounts of disease history, pain and functioning (condition-related variables) and the Bath Adolescent Pain Questionnaire (psychosocial variables). Correlation and regression analyses were used to establish influences on physical and social functioning, examining condition-related variables and psychosocial variables as separate blocks. Results Physical functioning was independently associated with age at onset, intensity of pain, presence of depression and pain-specific anxiety. Social functioning was only associated with general anxiety. The presence of an inflammatory diagnosis had no bearing on optimal functioning in this study. Conclusion Condition-related variables (age at onset, pain intensity) and psychosocial variables (depression, pain-specific anxiety) were equally important for physical functioning, whereas psychosocial variables (general anxiety) were more influential for social functioning. Understanding the impact of disease and associated variables in the adolescent rheumatology population should optimize targeted multidisciplinary rehabilitation for the young person and their family.

Total synthesis of the polyhydroxy caprolactam amide natural product, bengamide E, is accomplished starting from tartaric acid. Key reactions in the synthesis include desymmetrization of the bis(dimethylamide) unit of tartaric acid, Zn(BH(4))(2)-mediated anti-selective reduction, and a Horner-Wadsworth-Emmons olefination.

A facile ring opening of furans in furyl propargyl alcohols to the corresponding saturated gamma-keto esters is observed in the gold(III) chloride catalyzed reaction with MeOH. It is found that the ring opening of furan is driven by the intramolecular hydroalkoxylation. Mitigating the intramolecular hydroalkoxylation led to the expected conjugated enyne resulting from the dehydration. (C) 2015 Elsevier Ltd. All rights reserved.

A facile general route for the synthesis of azepino[4,5-b]indolones is presented. The strategy involves a Bronsted acid assisted intramolecular cyclization of unsaturated tryptamides. The methodology developed has been applied to the synthesis of the ABCD tetracyclic core of the natural product tronocarpine.

The isopropenyl substituted starting compounds (I) are prepared in a 3 step sequence starting from a known, geraniol-derived building block.

The enantiospecific total synthesis of 14-membered macrolactone Sch 725674 was accomplished from tartaric acid. Key reactions in the synthesis include the Ley's dithiaketalization of an alkynone derived from the bis-Weinreb amide of tartaric acid, Boord olefination, and ring-closing metathesis of an acrylate ester.

An enantiospecific total synthesis of polyhydroxy δ-pyrone natural product (+)-anamarine is accomplished. The main features of the synthesis include the stereoselective reduction of the ketone obtained by the desymmetrization of the bis-dimethyl amide of tartaric acid and further elaboration involving asymmetric Brown's allylation and ring closing metathesis.

An enantioselective synthesis of the macrolactone core of natural product Sch725674 was accomplished from furfural. Key reactions in assembly of the macrolactone are the use of furan as a but-2-ene-dione equivalent and ring closing metathesis.

The enantioselective alkylation of aldehydes with diethylzinc is achieved in the presence of a chiral sulfinamide as optimal catalyst.

Synthesis of isochromanones and isoquinolones comprising a quaternary center with high diastereoselectivity was realized via a AuCl3 catalyzed tandem intramolecular exo-dig heterocyclization/enol isomerization/Claisen rearrangement sequence in excellent yields. The reaction is general and amenable for the synthesis of structurally diverse analogues.

The enantiodivergent formal syntheses of both enantiomers of aspercyclide C is accomplished. Starting from L-(+)-tartaric acid, the key protected allylic alcohol, (3R,4R)-4-(methoxy-methoxy) non-1-en-3-ol is prepared, and is then elaborated into both enantiomers of 3-(4-methoxybenzyl)oxy]non-1-en-4-ol via Mitsunobu inversion. Esterification with a known biaryl acid, followed by ring-closing metathesis and deprotection completes the syntheses.

Various dialkoxides of zinc, magnesium and boron were examined for the enantioselective addition of diethylzinc to aryl aldehydes. Only zinc based reagent catalysed the reaction effectively providing up to 89% ee of the product.

[reaction: see text] Diels-Alder reactions of enantiomerically enriched 2H-azirine 3-phosphonates and dienes stereoselectively furnish optically pure, bicyclic aziridine adducts that on hydrogenation afford the first examples of enantiopure quaternary piperidine phosphonates.

An efficient approach to the aromatic sesquiterpene cuparene has been described starting from the readily available β‐ionone and employing a combination of epoxide rearrangement‐based ring‐contraction and ring‐closing metathesis reactions as key steps.

The addition of potassium dialkyl phosphites to enantiopure O-protected alpha-hydroxy sulfinimine pseudoenantiomers affords beta-hydroxy alpha-amino phosphonates in good yield and de. The reaction exhibits a strong match-mismatch effect.

[reaction: see text] N-Sulfinyl beta-amino Weinreb amides are prepared by condensation of sulfinimines with the potassium enolate of N-methoxy-N-methylacetamide. These new chiral building blocks are useful for the asymmetric synthesis of beta-amino carbonyl compounds, as illustrated here by the concise enantioselective syntheses of sedum alkaloids (+)-sedridine and (-)-allosedridine.