Stereochemical Study of a Transannular Michael Reaction Cascade

We systematically explored a transannular Michael reaction cascade for stereoselective synthesis of polycyclic systems. Both <i>E,Z</i>- and <i>E,E</i>-1,7-bis-enones in the form of 14-membered macrocyclic lactones underwent transannular cyclization to give polycyclic products with high efficiency and excellent diastereoselectivity. In contrast, <i>Z,E</i>- and <i>Z,Z</i>-macrocyclic lactones did not cyclize under similar reaction conditions. Our study revealed similarities and subtle stereochemical differences between this transannular cyclization process and transannular Diels–Alder reactions. An acyl ketene approach was developed for efficient synthesis of macrocyclic lactones. This investigation also illuminated the scope and limitation of macrocyclization by intramolecular Reformatsky reaction to prepare macrocyclic lactones

Stereochemical Study of a Transannular Michael Reaction Cascade

We systematically explored a transannular Michael reaction cascade for stereoselective synthesis of polycyclic systems. Both <i>E,Z</i>- and <i>E,E</i>-1,7-bis-enones in the form of 14-membered macrocyclic lactones underwent transannular cyclization to give polycyclic products with high efficiency and excellent diastereoselectivity. In contrast, <i>Z,E</i>- and <i>Z,Z</i>-macrocyclic lactones did not cyclize under similar reaction conditions. Our study revealed similarities and subtle stereochemical differences between this transannular cyclization process and transannular Diels–Alder reactions. An acyl ketene approach was developed for efficient synthesis of macrocyclic lactones. This investigation also illuminated the scope and limitation of macrocyclization by intramolecular Reformatsky reaction to prepare macrocyclic lactones

Stereochemical Study of a Transannular Michael Reaction Cascade

We systematically explored a transannular Michael reaction cascade for stereoselective synthesis of polycyclic systems. Both <i>E,Z</i>- and <i>E,E</i>-1,7-bis-enones in the form of 14-membered macrocyclic lactones underwent transannular cyclization to give polycyclic products with high efficiency and excellent diastereoselectivity. In contrast, <i>Z,E</i>- and <i>Z,Z</i>-macrocyclic lactones did not cyclize under similar reaction conditions. Our study revealed similarities and subtle stereochemical differences between this transannular cyclization process and transannular Diels–Alder reactions. An acyl ketene approach was developed for efficient synthesis of macrocyclic lactones. This investigation also illuminated the scope and limitation of macrocyclization by intramolecular Reformatsky reaction to prepare macrocyclic lactones

Stereochemical Study of a Transannular Michael Reaction Cascade

We systematically explored a transannular Michael reaction cascade for stereoselective synthesis of polycyclic systems. Both <i>E,Z</i>- and <i>E,E</i>-1,7-bis-enones in the form of 14-membered macrocyclic lactones underwent transannular cyclization to give polycyclic products with high efficiency and excellent diastereoselectivity. In contrast, <i>Z,E</i>- and <i>Z,Z</i>-macrocyclic lactones did not cyclize under similar reaction conditions. Our study revealed similarities and subtle stereochemical differences between this transannular cyclization process and transannular Diels–Alder reactions. An acyl ketene approach was developed for efficient synthesis of macrocyclic lactones. This investigation also illuminated the scope and limitation of macrocyclization by intramolecular Reformatsky reaction to prepare macrocyclic lactones

Empirical type-I error rate (for SNPs underlined) and power with and without bias correction in the presence of 30% invalid IVs.

Sample standard deviations (SD) are given in parenthesis.</p

True values and mean estimates of <i>b</i> with <i>ρ</i> = 0 and 30% invalid IVs.

Sample standard deviations (SD), mean standard errors (Mean SE) are given in parenthesis.</p

Supplementary file with theory and derivations/proofs, more simulation results and additional real data analysis results.

Supplementary file with theory and derivations/proofs, more simulation results and additional real data analysis results.</p

Manhattan plot of BMI before (upper panel) and after (lower panel) applying MVMR-cML bias correction (in <i>M</i>₁).

(a): one metabolomic PC is adjusted, (b): two metabolomic PCs are adjusted, (c): five metabolomic PCs are adjusted.</p

Mean estimates of the effects of SNPs having collider bias with <i>ρ</i> = 0 and 30% invalid IVs.

Horizontal coordinates are for the true effects, vertical coordinates are for the estimated effects. Vertical bars are the means of standard errors averaged over 1000 repetitions. In the legends, “H only” means the SNPs affecting only the covariates; “H and Y” means the SNPs affecting both the covariates and outcome. (a)-(b): p2 = 1; (c)-(d): p2 = 2; (e)-(f): p2 = 4.</p

Directed acyclic graph for outcome <i>Y</i>, SNP <i>G</i>_<i>i</i>, covariates <i>H</i> and <i>J</i>, and confounder <i>U</i>.

Conditioning on the colliders H1 and H2 induces a conditional association between Gi and U, represented by the dashed line. This creates an indirect association between Gi and Y through the path Gi → U → Y, which will bias the estimation of the direct effect . J1 and J2 are not associated with Gi and U, and therefore do not introduce bias.</p