Daesung Lee

Cyclization initiated by hydrogen bonding-directed 1,6/1,4-addition of nucleophiles onto 1,3-diynyl ketones, yielding formal enyne ring-closing metathesis products and indanone derivatives, is described.

Figure S5. Changes in signaling in BM of trisomy 8+ TN-MF patient and MYC MF mice. Figure S6. Effects of silencing S100a9 in MYC-driven MF or overexpression of S100a9. Figure S7. Effects of inhibition of S100a9 or MYC in MYC-driven MF. Figure S8. Synthesis and Characterization of Tasquinimod. Figure S9. Synthesis and Characterization of MYCi975.

Comparison of gene expression profiles of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC vs. Mx1-Cre+/-;Rosa26+/+ mouse.

Cell-cell interaction analyses.

Figure S1. Landscape of somatic mutations and cytogenetics in Moffitt MF cohort. Figure S2. Effects of enforced MYC expression in HSCs in vivo. Figure S3. MYC-induced changes in hematopoietic sub-populations and colony forming potential. Figure S4. The JAK/STAT, PI3K/AKT, MEK/ERK, and alarmin pathways in MYC-driven MF.

Table S1. Demographics of Moffitt Total Cancer Care MF patients. Table S2. Demographic Profile of trisomy 8+ TN-MF patients and HDs used in scRNA-seq analysis and PDX studies. Table S3. List of genes used for PROGENy analysis of human BM cells. Table S4. Demographics of TN-MF patients. Table S5. Clinical parameters of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC studies. Table S6. Clinical parameters of Scl-CreERT+/-;Rosa26LSL-MYC/LSL-MYC in vivo studies. Table S7. Clinical parameters in competitive transplant studies. Table S8. Comparison of gene expression profiles of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC vs. Mx1-Cre+/-;Rosa26+/+ mouse. Table S9. List of genes used for PROGENy analysis of mouse BM cells. Table S10. Cell-cell interaction analyses. Table S11. Clinical parameters of Mx1-Cre+/-;Rosa26LSL-MYC/LSL-MYC;S100a9-/- studies. Table S12. Clinical parameters of S100a9 transgenic mouse studies. Table S13. Clinical parameters of Tasquinimod efficacy studies in MYC-driven MF. Table S14. Clinical parameters of MYCi975 efficacy studies in MYC-driven MF. Table S15: Key Resources Table. Table S16: Sequence Information.

Efficient Diels–Alder dimerizations of ene-allenes and enyne-allenes to generate highly functionalized spirocycles with good chemo-, regio-, and stereo-selectivities, supported by DFT studies, are described.

The alkyne 1,2-difunctionalization represents a versatile transformation whereby one or both of the π-bonds of the alkyne are engaged in bond-forming processes to generate products that contain newly formed C–C or C–heteroatom bonds at both carbons.

We report herein a concise route for the total synthesis of rapicone. The key strategy to form the ynone intermediate involves an Fe(III)/TEMPO-catalyzed aerobic oxidation of a 1,3-dihydroisobenzofuran moiety. This ether oxidation for the simultaneous installation of the keto aldehyde allowed the effective formation of the required ynone intermediate. The concise total synthesis of rapicone is substantiated by the unique formal [4 + 2] cycloaddition of acyl ketene with alkynone and is completed in 7 steps with 9.4% overall yield.

We describe novel amine‐mediated transformation of alkynyl ketones and amides to generate 2‐methylene‐2H‐pyrans, substituted 3‐hydroxy‐9H‐fluoren‐9‐ones, and amine‐incorporated arenes. These cascade processes are initiated by conjugate addition of secondary amine followed by hydrolysis of the enamine/vinylogous amide intermediates. The product distribution is highly sensitive to the steric and electronic effects of the substituents on both the alkyne moieties, the tether structure connecting them, and the nature of the amine. Alkynyl amide participates in the Alder‐ene reaction favorably to generate more reactive allene amide that reacts with amine to generate amine‐incorporated arene products. These metal‐free cascade reactions are a useful synthetic method that can be exploited for the construction of various hetero‐ and carbocyclic systems.