Preparation of Functional Phosphorus Zwitterions from Activated Alkanes, Aldehydes, and Tributylphosphine: Synthesis of Polysubstituted Furo[3,2-<i>c</i>]coumarins

A general preparation of new types of highly functional phosphorus zwitterions is realized via tandem three-component reactions using the corresponding functional alkanes, aldehydes, and Bu₃P. Starting from our novel zwitterions as synthetic reagents with commercially available acid chlorides in a one-step procedure provides an attractive approach toward furo[3,2-<i>c</i>]coumarins

Preparation of Functional Phosphorus Zwitterions from Activated Alkanes, Aldehydes, and Tributylphosphine: Synthesis of Polysubstituted Furo[3,2-<i>c</i>]coumarins

A general preparation of new types of highly functional phosphorus zwitterions is realized via tandem three-component reactions using the corresponding functional alkanes, aldehydes, and Bu₃P. Starting from our novel zwitterions as synthetic reagents with commercially available acid chlorides in a one-step procedure provides an attractive approach toward furo[3,2-<i>c</i>]coumarins

Organocatalytic Enantioselective Synthesis of Tetrahydrofluoren-9-ones via Vinylogous Michael Addition/Henry Reaction Cascade of 1,3-Indandione-Derived Pronucleophiles

An unprecedented organocatalytic enantioselective vinylogous Michael addition/Henry cyclization cascade is presented for the synthesis of highly substituted tetrahydrofluoren-9-ones <b>3</b> employing novel 1,3-indandione-derived pronucleophiles <b>1a</b>–<b>g</b> and nitroalkenes <b>2</b>. Following a very simple protocol, a wide range of products were obtained in good to excellent yields and with excellent enantioinduction (43–98% yield, up to 98% ee). The reaction proceeded with excellent diastereocontrol despite the simultaneous generation of four stereogenic centers. Surprisingly, when 2-(1-phenylethylidene)-1<i>H</i>-indandione (<b>1h</b>) was used as a pronucleophile, no cyclization was observed, and only Michael addition adducts <b>4a</b>–<b>x</b> were furnished in very good yields and excellent enantioselectivities

Expanding the Scope of Primary Amine Catalysis: Stereoselective Synthesis of Indanedione-Fused 2,6-Disubstituted <i>trans-</i>Spirocyclohexanones

A cinchona-alkaloid-derived chiral primary-amine-catalyzed enantioselective method for the synthesis of the thermodynamically less stable indanedione-fused 2,6-<i>trans</i>-disubstituted spirocyclohexanones is demonstrated. Both the enantiomeric forms of the <i>trans</i> isomer are obtained in excellent yields and enantioselectivities. Furthermore, one of the enantiopure <i>trans</i>-spiranes bearing an additional α-substitution on the cyclohexanone ring was then epimerized into its thermodynamically stable <i>cis</i> counterpart, with little loss of enantioselectivity to demonstrate the feasibility of such a transformation. Mechanistic investigations revealed two competing pathways, a concerted Diels–Alder reaction and a stepwise Michael addition, for the formation of corresponding products

Synthesis of Functionalized Furans via Chemoselective Reduction/Wittig Reaction Using Catalytic Triethylamine and Phosphine

An efficient protocol for the synthesis of highly functionalized furans via intramolecular Wittig reaction has been developed using catalytic amounts of phosphine and triethylamine. Silyl chloride served as the initial promoter to activate the phosphine oxide. Reduction of the activated phosphine oxide by hydrosilane resulted in generation of phosphine, while decomposition of Et₃N·HCl resulted in regeneration of base, which mediated formation of phosphorus ylide. Remarkably, the in situ generated byproduct, Et₃N·HCl, also catalyzes reduction of phosphine oxide

Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and Beyond

The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4⁺ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., <b>16</b>) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug <b>1</b> (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound <b>16</b> into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor–ligand interactions for further structural modifications

Development of Stem-Cell-Mobilizing Agents Targeting CXCR4 Receptor for Peripheral Blood Stem Cell Transplantation and Beyond

The function of the CXCR4/CXCL12 axis accounts for many disease indications, including tissue/nerve regeneration, cancer metastasis, and inflammation. Blocking CXCR4 signaling with its antagonists may lead to moving out CXCR4⁺ cell types from bone marrow to peripheral circulation. We have discovered a novel series of pyrimidine-based CXCR4 antagonists, a representative (i.e., <b>16</b>) of which was tolerated at a higher dose and showed better HSC-mobilizing ability at the maximal response dose relative to the approved drug <b>1</b> (AMD3100), and thus considered a potential drug candidate for PBSCT indication. Docking compound <b>16</b> into the X-ray crystal structure of CXCR4 receptor revealed that it adopted a spider-like conformation striding over both major and minor subpockets. This putative binding mode provides a new insight into CXCR4 receptor–ligand interactions for further structural modifications