Few classes of natural products rival
the structural audacity of
oligosaccharides. Their complexity, however, has stood as an immense
roadblock to translational research, as access to homogeneous material
from nature is challenging. Thus, while carbohydrates are critical
to the myriad functional and structural aspects of the biological
sciences, their behavior is largely descriptive. This challenge presents
an attractive opportunity for synthetic chemistry, particularly in
the area of human milk science. First, there is an inordinate need
for synthesizing homogeneous human milk oligosaccharides (HMOs). Superimposed
on this goal is the mission of conducting syntheses at scale to enable
animal studies. Herein, we present a personalized rumination of our
involvement, and that of our colleagues, which has led to the synthesis
and characterization of HMOs and mechanistic probes. Along the way,
we highlight chemical, chemoenzymatic, and synthetic biology based
approaches. We close with a discussion on emergent challenges and
opportunities for synthesis, broadly defined, in human milk science.