Convenient preparation and use of a new analytical construct for the analysis and development of solid-phase chemistries

An expedient and scalable synthesis of a versatile new analytical construct intermediate 1 is described. The utility of the intermediate 1 is exemplified by the preparation of the construct resin 14 incorporating an acid-labile linker which is used to conveniently develop optimized conditions leading to the preparation of a small compound array 24(1-3,1-3). The optimized conditions are shown to work equally well on both the construct resin 14 and the corresponding base resin 15.     

Synthesis of a first thiophene containing analog of the HIV protease inhibitor nelfinavir

A stereoselective and efficient preparation of a thiophene containing intermediate 2 from ethyl 3-thienyl propenoate 4 as the core of new possible HIV protease inhibitors is described. The chiral intermediate has been successfully used for the preparation of the analog 1 of the potent HIV inhibitor nelfinavir.     

Second-generation synthesis of protected phosphonothiodifluoromethylene analogues of nucleoside-3′-phosphates

A practical, eight-step synthesis of the key intermediate 14 in 19% overall yield from α-d-xylose is described. The preparation can be carried out on multi-gram scale and involves the use of the organomagnesium reagent 2d. The capability of derivative 14 to be transformed into the title compounds is examplified by the preparation of 15. Additionally, X-ray crystallography of intermediate 12 provided the first structural data on difluorophosphonothioates.     

Preparation of unsubstituted dipyridine‐dibarbituric acid ylide through dimerization of pyridin‐2‐ylmethylenepyrimidinetrione as a reactive intermediate

Preparation of 5,5′‐(pyridin‐2‐ylmethylene)dipyrimidinetrione from barbituric acid and 2‐pyridinecarbox‐aldehyde in any polar solvent is a straightforward synthetic procedure, while preparation of the dipyridine‐dibarbituric acid ylide from the same starting materials is sensitive to the reaction media, pH, and temperature. For both products, the formation of the reactive intermediate 2‐pyridin‐2‐ylmethylenepyrimidinetrione is certain and this intermediate is a cross road for the reaction to be directed in one way or other. The experimental evidence for the formation of this important intermediate, as well as synthetic procedures for the preparation of both condensation products are presented.     

Synthesis of N,O-disubtituted 3-hydroxymethyl-7-Aminocephalosporanic acid

A method has been developed for the preparation of tert-butoxycarbonylandno-3-hydroxymethylceph-2-em-4-carboxylic acid, which is an intermediate for the preparation of new antibiotic derivatives with antibacterial, anti-inflammatory, or antitumor activity.     

The preparation of (±) 18,19-epoxy-14,15,16-trisnorclerodan-13-oic acid as a key intermediate in the total synthesis of clerodane type diterpenes

The stereospecific preparation of (±) 18,19-epoxy-14,15,16-trisnorclerodan-13-oic acid is described. This compound can serve as a key intermediate in the preparation of clerodane diterpenes as it possesses the right stereochemistry at all asymmetric centres.     

Toward the synthesis of (+)-peloruside A via an intramolecular vinylogous aldol reaction

The use of the intramolecular vinylogous aldol reaction for the preparation of an advanced intermediate for the synthesis of peloruside A is described. The reaction was applied to compound 19 and proceeds in high yield and good levels of diastereoselectivity. Application of the Achmatowicz reaction to this intermediate provided the corresponding pyranone, a late stage intermediate well positioned for conversion to the natural product.     

New acyl anion equivalent. A short route to the enol lactam intermediate in cytochalasin synthesis

The preparation and Emmons-Horner reactions of various α-alkoxyphosphonoacetates were examined. The latter reactions proceeded with considerable stereoselectivity, which allowed the efficient preparation of an intermediate in cytochalasin synthesis.     

A divergent approach to apoptolidin and FD-891: asymmetric preparation of a common intermediate

Biologically active Apoptolidin and FD-891 have structural similarity in their macrocyclic cores. Asymmetric preparation of a common intermediate in the total synthesis of these two macrolides is presented. A modified Masuyama Sn-allylation was employed to control the relative stereochemistry in the synthesis of the intermediate.     

Highly Diastereoselective Alkylation of a Pyroglutamate Derivative with an Electrophile Obtained from Indole. Synthesis of a Potential Intermediate for the Preparation of the Natural Sweetener (-)-Monatin

The synthesis of a potential intermediate for the preparation of the very intensive sweetening agent (-)-Monatin is described. The synthesis is based on a highly diastereoselective alkylation reaction of a pyroglutamate derivative with an electrophile obtained from indole.     

Synthesis of the taxane diterpenes: Construction of a bc ring intermediate for taxane synthesis

A general and practical route to a crucial BC ring intermediate for the preparation of simple taxanes is described.     

Synthesis of natural ecteinascidins (ET-729, ET-745, ET-759B, ET-736, ET-637, ET-594) from cyanosafracin B

The semisynthetic process initially described for the synthesis of 1 (ET-743) has been extended to the preparation of other natural ecteinascidins. For the synthesis of 2 (ET-729) a demethylation of a N-Me intermediate was carried out by a selective oxidation with MCPBA. Other natural ecteinascidins (ET-745, ET-759B, ET-736, ET-637, ET-594) were accessible from key intermediate 25. The described methodologies allow for the preparation of a wide variety of ecteinascidins by procedures that can be easily scaled up.     

Stereo-selective synthesis of Erythro-3-methyl-hexyn-3,4-diol

A very short stereo-selective preparation of the title compound, an intermediate of methynolide synthesis, is described.     

Synthesis of the 2-aza-7-oxatricyclo[4.3.2.04,8]undecane nucleus of some gelsemium alkaloids

The preparation of a key tricyclic intermediate for the eventual total synthesis of the alkaloids gelsemicine and gelsedine is described.     

A novel synthesis of guanine PDE inhibitors via tricyclic imidazopyrimidines

A new method for the preparation of developmental tetracyclic guanine PDE inhibitors via a common tricyclic pyrimidine intermediate is described.     

Methodology for the preparation of 2-argininylbenzothiazole

An efficient process to produce kilogram quantities of a key argininylbenzo[d]thiazole intermediate was developed for the preparation of the tryptase inhibitor RWJ-56423. A variety of activated arginine esters and benzo[d]thiazole nucleophiles were evaluated as coupling partners. Our work led to the selection and optimization of an argininyl imidazolide ester and benzothiazol-2-yl MgCl nucleophile. This paper focuses on the preparation, use, and stability of the benzothiazol-2-yl Grignard reagents.     

Facile One-Pot Synthesis of Novel Tricyclic Dibenzoheterocycles via the Dianion Protocol of Ditopic Ligands

In our ongoing studies on the synthesis of new heterocyclic ring systems via a dianion intermediate, we herein describe the preparation of novel dibenzoazadioxoninone, dibenzoazadioxoninethione, dibenzoazadioxocine, dibenzoazadioxacycloundecine, dibenzoazadioxacyclododecine, dibenzoaza-2-oxodioxaphosphonine, and dibenzoaza-2-oxo-1,3-thioxaphosphonine in good yields.     

Synthesis and antioxidant activity of 5-hydroxycoumarans, 6-hydroxychromanes and sulfur-containing derivatives on their base

A synthesis of 5-hydroxycoumarans, 6-hydroxychromanes and their dodecylthiomethylsubstituted derivatives was accomplished based on methylphenols through the intermediate preparation of 2-allyl-4-alkoxyphenols. The sulfur-containing compounds synthesized were shown to be highly efficient as inhibitors of autooxidation of methyl oleate.     

A concise synthesis of 7-chloro-2-methylsulfanyl-thiazolo[4,5-b]pyridine-6-carbonitrile, a versatile intermediate for substituted 6-cyanothiazolopyridines

We describe the development of a simple route for the preparation of the novel title intermediate thiazolo[4,5-b]pyridine. This intermediate was particularly well suited for derivatization at the C-2 and C-7 positions of the bicyclic ring system.     

Progress towards the synthesis of papuaforin A: selective formation of α-bromoenones from silyl enol ethers

The selective one-pot conversion of enol silyl ethers into α-bromoenones allows a direct preparation of a tricyclic intermediate to papuaforin A.